A novel variant of C12orf4 in a consanguineous Armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype
Background Intellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic variants in a specific gene are found only in a small number of patients, and difficulties arise in the definition of prevailing genotype and ch...
Saved in:
Published in | Molecular genetics & genomic medicine Vol. 7; no. 9; pp. e865 - n/a |
---|---|
Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
John Wiley & Sons, Inc
01.09.2019
John Wiley and Sons Inc Wiley |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Background
Intellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic variants in a specific gene are found only in a small number of patients, and difficulties arise in the definition of prevailing genotype and characteristic phenotype associated with that gene. One of such very rare disorders is autosomal recessive ID type 66 (OMIM #618221) caused by defects in C12orf4. Up to now, six families have been reported with mostly truncating variants. The spectrum of the clinical phenotype was not emphasized in previous reports, and detailed phenotype was not always available from previous patients, especially from large cohort studies.
Methods
Exome sequencing was performed in a consanguineous Armenian family with two affected adult brothers.
Results
The patients carry a novel homozygous nonsense C12orf4 variant. The integration of previous data and phenotyping of the brothers indicate that the clinical picture of C12orf4 defects involves hypotonia in infancy, rather severe ID, speech impairment, and behavioral problems such as aggressiveness, unstable mood, and autistic features. Several other symptoms are more variable and less consistent.
Conclusion
This rather nonsyndromic and nonspecific clinical picture implies that additional patients with C12orf4 defects will likely continue to be identified using the “genotype‐first” approach, rather than based on clinical assessment. The phenotype needs further delineation in future reports.
Intellectual disability (ID) is caused by thousands of genes and variants in a specific gene are found only in a small number of patients. Up to now, six families have been reported with C12orf4 defects causing autosomal recessive ID type 66 (OMIM #618221). Our finding of a novel homozygous nonsense C12orf4 variant in two adult brothers from a consanguineous Armenian family supports the disease association of C12orf4 and shows that its defects cause hypotonia in infancy, rather severe ID, speech impairment, and behavioral problems (aggressiveness, unstable mood, and autistic features), while other symptoms are more variable and less consistent. |
---|---|
AbstractList | BackgroundIntellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic variants in a specific gene are found only in a small number of patients, and difficulties arise in the definition of prevailing genotype and characteristic phenotype associated with that gene. One of such very rare disorders is autosomal recessive ID type 66 (OMIM #618221) caused by defects in C12orf4. Up to now, six families have been reported with mostly truncating variants. The spectrum of the clinical phenotype was not emphasized in previous reports, and detailed phenotype was not always available from previous patients, especially from large cohort studies.MethodsExome sequencing was performed in a consanguineous Armenian family with two affected adult brothers.ResultsThe patients carry a novel homozygous nonsense C12orf4 variant. The integration of previous data and phenotyping of the brothers indicate that the clinical picture of C12orf4 defects involves hypotonia in infancy, rather severe ID, speech impairment, and behavioral problems such as aggressiveness, unstable mood, and autistic features. Several other symptoms are more variable and less consistent.ConclusionThis rather nonsyndromic and nonspecific clinical picture implies that additional patients with C12orf4 defects will likely continue to be identified using the “genotype‐first” approach, rather than based on clinical assessment. The phenotype needs further delineation in future reports. Abstract Background Intellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic variants in a specific gene are found only in a small number of patients, and difficulties arise in the definition of prevailing genotype and characteristic phenotype associated with that gene. One of such very rare disorders is autosomal recessive ID type 66 (OMIM #618221) caused by defects in C12orf4. Up to now, six families have been reported with mostly truncating variants. The spectrum of the clinical phenotype was not emphasized in previous reports, and detailed phenotype was not always available from previous patients, especially from large cohort studies. Methods Exome sequencing was performed in a consanguineous Armenian family with two affected adult brothers. Results The patients carry a novel homozygous nonsense C12orf4 variant. The integration of previous data and phenotyping of the brothers indicate that the clinical picture of C12orf4 defects involves hypotonia in infancy, rather severe ID, speech impairment, and behavioral problems such as aggressiveness, unstable mood, and autistic features. Several other symptoms are more variable and less consistent. Conclusion This rather nonsyndromic and nonspecific clinical picture implies that additional patients with C12orf4 defects will likely continue to be identified using the “genotype‐first” approach, rather than based on clinical assessment. The phenotype needs further delineation in future reports. Intellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic variants in a specific gene are found only in a small number of patients, and difficulties arise in the definition of prevailing genotype and characteristic phenotype associated with that gene. One of such very rare disorders is autosomal recessive ID type 66 (OMIM #618221) caused by defects in C12orf4. Up to now, six families have been reported with mostly truncating variants. The spectrum of the clinical phenotype was not emphasized in previous reports, and detailed phenotype was not always available from previous patients, especially from large cohort studies. Exome sequencing was performed in a consanguineous Armenian family with two affected adult brothers. The patients carry a novel homozygous nonsense C12orf4 variant. The integration of previous data and phenotyping of the brothers indicate that the clinical picture of C12orf4 defects involves hypotonia in infancy, rather severe ID, speech impairment, and behavioral problems such as aggressiveness, unstable mood, and autistic features. Several other symptoms are more variable and less consistent. This rather nonsyndromic and nonspecific clinical picture implies that additional patients with C12orf4 defects will likely continue to be identified using the "genotype-first" approach, rather than based on clinical assessment. The phenotype needs further delineation in future reports. Background Intellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic variants in a specific gene are found only in a small number of patients, and difficulties arise in the definition of prevailing genotype and characteristic phenotype associated with that gene. One of such very rare disorders is autosomal recessive ID type 66 (OMIM #618221) caused by defects in C12orf4. Up to now, six families have been reported with mostly truncating variants. The spectrum of the clinical phenotype was not emphasized in previous reports, and detailed phenotype was not always available from previous patients, especially from large cohort studies. Methods Exome sequencing was performed in a consanguineous Armenian family with two affected adult brothers. Results The patients carry a novel homozygous nonsense C12orf4 variant. The integration of previous data and phenotyping of the brothers indicate that the clinical picture of C12orf4 defects involves hypotonia in infancy, rather severe ID, speech impairment, and behavioral problems such as aggressiveness, unstable mood, and autistic features. Several other symptoms are more variable and less consistent. Conclusion This rather nonsyndromic and nonspecific clinical picture implies that additional patients with C12orf4 defects will likely continue to be identified using the “genotype‐first” approach, rather than based on clinical assessment. The phenotype needs further delineation in future reports. Intellectual disability (ID) is caused by thousands of genes and variants in a specific gene are found only in a small number of patients. Up to now, six families have been reported with C12orf4 defects causing autosomal recessive ID type 66 (OMIM #618221). Our finding of a novel homozygous nonsense C12orf4 variant in two adult brothers from a consanguineous Armenian family supports the disease association of C12orf4 and shows that its defects cause hypotonia in infancy, rather severe ID, speech impairment, and behavioral problems (aggressiveness, unstable mood, and autistic features), while other symptoms are more variable and less consistent. |
Author | Stranecky, Viktor Sedlacek, Zdenek Midyan, Susanna Babikyan, Davit Bendova, Sarka Sarkisian, Tamara Hancarova, Miroslava Shahsuvaryan, Gohar Prchalova, Darina |
AuthorAffiliation | 3 Department of Pediatrics and Adolescent Medicine Charles University 1st Faculty of Medicine and General University Hospital Prague Czech Republic 1 Department of Biology and Medical Genetics Charles University 2nd Faculty of Medicine and University Hospital Motol Prague Czech Republic 2 Department of Medical Genetics Yerevan State Medical University after Mkhitar Heratsi, and Center of Medical Genetics and Primary Health Care Yerevan Armenia |
AuthorAffiliation_xml | – name: 1 Department of Biology and Medical Genetics Charles University 2nd Faculty of Medicine and University Hospital Motol Prague Czech Republic – name: 3 Department of Pediatrics and Adolescent Medicine Charles University 1st Faculty of Medicine and General University Hospital Prague Czech Republic – name: 2 Department of Medical Genetics Yerevan State Medical University after Mkhitar Heratsi, and Center of Medical Genetics and Primary Health Care Yerevan Armenia |
Author_xml | – sequence: 1 givenname: Miroslava orcidid: 0000-0001-6772-8862 surname: Hancarova fullname: Hancarova, Miroslava organization: Charles University 2nd Faculty of Medicine and University Hospital Motol – sequence: 2 givenname: Davit surname: Babikyan fullname: Babikyan, Davit organization: Yerevan State Medical University after Mkhitar Heratsi, and Center of Medical Genetics and Primary Health Care – sequence: 3 givenname: Sarka surname: Bendova fullname: Bendova, Sarka organization: Charles University 2nd Faculty of Medicine and University Hospital Motol – sequence: 4 givenname: Susanna surname: Midyan fullname: Midyan, Susanna organization: Yerevan State Medical University after Mkhitar Heratsi, and Center of Medical Genetics and Primary Health Care – sequence: 5 givenname: Darina surname: Prchalova fullname: Prchalova, Darina organization: Charles University 2nd Faculty of Medicine and University Hospital Motol – sequence: 6 givenname: Gohar surname: Shahsuvaryan fullname: Shahsuvaryan, Gohar organization: Yerevan State Medical University after Mkhitar Heratsi, and Center of Medical Genetics and Primary Health Care – sequence: 7 givenname: Viktor surname: Stranecky fullname: Stranecky, Viktor organization: Charles University 1st Faculty of Medicine and General University Hospital – sequence: 8 givenname: Tamara surname: Sarkisian fullname: Sarkisian, Tamara organization: Yerevan State Medical University after Mkhitar Heratsi, and Center of Medical Genetics and Primary Health Care – sequence: 9 givenname: Zdenek orcidid: 0000-0001-6575-9163 surname: Sedlacek fullname: Sedlacek, Zdenek email: zdenek.sedlacek@lfmotol.cuni.cz organization: Charles University 2nd Faculty of Medicine and University Hospital Motol |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31334606$$D View this record in MEDLINE/PubMed |
BookMark | eNp1ksFu1DAQQCNUREupxBcgS1y4pDhx4iQXpNUKlkpFXOBs2c4465VjL7azVT6q_4izW0qLhC-2xk_PM-N5nZ1ZZyHL3hb4usC4_DgOA7luaf0iuyhJWeVdSbuzJ-fz7CqEHU6rbauCNq-yc1IQUlFML7L7FbLuAAYduNfcRuQUWhel86pC2iKOpLOB22HSFtwU0MqPYBOIFB-1mZdrpf0YUNwCgqidccO8SPgUXXAjN8iDhBD0AZIwgjEg45TCvQ5caKPjjOK8B0QputNxi3ow6S2eVHbxLN79FqxboDfZS8VNgKuH_TL7-eXzj_XX_Pb75ma9us1ljas6F2VZC0VANqoWNU_VilQ4CEorTHDfSpA1F01LqqbvitSimnbQEy44KCqhJpfZzcnbO75je69H7mfmuGbHgPMD4z5qaYA1QLCSLSWVbKuGd6IrKpVksmtEpQRPrk8n134SI_QSbPTcPJM-v7F6ywZ3YLQhZdm2SfDhQeDdrwlCZKMOMjWSH7-EJaipCW7LJe_3_6A7N3mbWnWkcEHbpvkrlN6F4EE9JlNgtowUW0aKpZFK6LunyT-CfwYoAfkJuNMG5v-K2LfNhizC38_p2to |
CitedBy_id | crossref_primary_10_1016_j_molcel_2023_05_012 crossref_primary_10_1002_jgm_3406 |
Cites_doi | 10.1016/j.celrep.2014.12.015 10.1016/j.ajhg.2016.03.016 10.1016/j.ajhg.2016.01.016 10.1038/nature19057 10.1111/cge.12821 10.1016/j.ridd.2010.12.018 10.1186/s12881-017-0425-4 10.1038/s41380-017-0012-2 10.1371/journal.pone.0104998 10.1016/j.cell.2015.09.053 10.1681/ASN.2009111104 10.1038/s41436-018-0138-x 10.1038/mp.2017.60 10.1016/j.tig.2016.01.001 10.1212/NXG.0000000000000076 10.1038/ng.2405 10.1007/s11825-018-0209-z 10.1038/onc.2014.406 10.1001/jamapsychiatry.2016.3798 |
ContentType | Journal Article |
Copyright | 2019 The Authors. published by Wiley Periodicals, Inc. 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. 2019. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
Copyright_xml | – notice: 2019 The Authors. published by Wiley Periodicals, Inc. – notice: 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. – notice: 2019. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
DBID | 24P WIN CGR CUY CVF ECM EIF NPM AAYXX CITATION 7QO 8FD 8FE 8FH ABUWG AFKRA AZQEC BBNVY BENPR BHPHI CCPQU DWQXO FR3 GNUQQ HCIFZ LK8 M7P P64 PIMPY PQEST PQQKQ PQUKI PRINS RC3 7X8 5PM DOA |
DOI | 10.1002/mgg3.865 |
DatabaseName | Wiley Online Library Open Access Wiley Online Library website Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef Biotechnology Research Abstracts Technology Research Database ProQuest SciTech Collection ProQuest Natural Science Collection ProQuest Central (Alumni) ProQuest Central ProQuest Central Essentials Biological Science Collection ProQuest Central Natural Science Collection ProQuest One Community College ProQuest Central Korea Engineering Research Database ProQuest Central Student SciTech Premium Collection Biological Sciences Biological Science Database Biotechnology and BioEngineering Abstracts Publicly Available Content Database ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China Genetics Abstracts MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef Publicly Available Content Database ProQuest Central Student Technology Research Database ProQuest Biological Science Collection ProQuest Central Essentials ProQuest One Academic Eastern Edition ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest Natural Science Collection Biological Science Database ProQuest SciTech Collection ProQuest Central China Biotechnology and BioEngineering Abstracts ProQuest Central Genetics Abstracts Biotechnology Research Abstracts ProQuest One Academic UKI Edition Natural Science Collection ProQuest Central Korea Biological Science Collection Engineering Research Database ProQuest One Academic MEDLINE - Academic |
DatabaseTitleList | Publicly Available Content Database MEDLINE MEDLINE - Academic |
Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: 24P name: Wiley Open Access url: https://authorservices.wiley.com/open-science/open-access/browse-journals.html sourceTypes: Publisher – sequence: 3 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 4 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database – sequence: 5 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine |
DocumentTitleAlternate | HANCAROVA et al |
EISSN | 2324-9269 |
EndPage | n/a |
ExternalDocumentID | oai_doaj_org_article_7e30fc8634c847a9b914fed3c97b4fba 10_1002_mgg3_865 31334606 MGG3865 |
Genre | article Research Support, Non-U.S. Gov't Journal Article Case Reports Report Case Study |
GeographicLocations | Armenia |
GeographicLocations_xml | – name: Armenia |
GrantInformation_xml | – fundername: Ministry of Health of the Czech Republic funderid: 17-29423A – fundername: Ministry of Health of the Czech Republic grantid: 17-29423A |
GroupedDBID | 0R~ 1OC 24P 31~ 53G 5VS 8-1 8FE 8FH AAHHS AAZKR ABDBF ACCFJ ACXQS ADBBV ADKYN ADRAZ ADZMN AEEZP AEQDE AFKRA AIWBW AJBDE ALAGY ALMA_UNASSIGNED_HOLDINGS ALUQN AOIJS AVUZU BAWUL BBNVY BCNDV BENPR BHPHI CCPQU D-9 DIK EBS EJD GODZA GROUPED_DOAJ HCIFZ HYE HZ~ IAO IHR INH KQ8 LK8 M48 M7P M~E O9- OK1 PIMPY PROAC RPM TUS WIN CGR CUY CVF ECM EIF ITC NPM AAYXX CITATION 7QO 8FD ABUWG AZQEC DWQXO FR3 GNUQQ P64 PQEST PQQKQ PQUKI PRINS RC3 7X8 5PM ACUHS |
ID | FETCH-LOGICAL-c5045-b225bf3ec7f5b5a313b416eb664030d8cec5ab78347d91269569ed3abaef6ce53 |
IEDL.DBID | RPM |
ISSN | 2324-9269 |
IngestDate | Tue Dec 17 15:27:11 EST 2024 Tue Sep 17 21:16:28 EDT 2024 Sun May 12 00:27:38 EDT 2024 Thu Oct 10 19:47:26 EDT 2024 Fri Dec 06 02:53:01 EST 2024 Sat Sep 28 08:25:54 EDT 2024 Sat Aug 24 01:17:41 EDT 2024 |
IsDoiOpenAccess | true |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 9 |
Keywords | exome sequencing consanguinity C12orf4 intellectual disability |
Language | English |
License | Attribution-NonCommercial-NoDerivs 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c5045-b225bf3ec7f5b5a313b416eb664030d8cec5ab78347d91269569ed3abaef6ce53 |
Notes | Funding information Ministry of Health of the Czech Republic, Grant/Award Number: 17‐29423A. ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3 Miroslava Hancarova and Davit Babikyan should be considered joint first author. |
ORCID | 0000-0001-6772-8862 0000-0001-6575-9163 |
OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732288/ |
PMID | 31334606 |
PQID | 2287016877 |
PQPubID | 2034370 |
PageCount | 5 |
ParticipantIDs | doaj_primary_oai_doaj_org_article_7e30fc8634c847a9b914fed3c97b4fba pubmedcentral_primary_oai_pubmedcentral_nih_gov_6732288 proquest_miscellaneous_2287530825 proquest_journals_2287016877 crossref_primary_10_1002_mgg3_865 pubmed_primary_31334606 wiley_primary_10_1002_mgg3_865_MGG3865 |
PublicationCentury | 2000 |
PublicationDate | September 2019 |
PublicationDateYYYYMMDD | 2019-09-01 |
PublicationDate_xml | – month: 09 year: 2019 text: September 2019 |
PublicationDecade | 2010 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States – name: Bognor Regis – name: Hoboken |
PublicationTitle | Molecular genetics & genomic medicine |
PublicationTitleAlternate | Mol Genet Genomic Med |
PublicationYear | 2019 |
Publisher | John Wiley & Sons, Inc John Wiley and Sons Inc Wiley |
Publisher_xml | – sequence: 0 name: Wiley – name: John Wiley & Sons, Inc – name: John Wiley and Sons Inc |
References | 2015; 163 2015; 34 2010; 21 1993; 9 2017; 74 2017; 91 2016; 2 2016; 536 2019; 24 2015; 10 2016; 98 2016; 32 2011; 32 2018; 30 2017; 18 2018; 23 2014; 9 2018; 21 2012; 44 e_1_2_7_6_1 e_1_2_7_5_1 e_1_2_7_4_1 e_1_2_7_3_1 e_1_2_7_9_1 e_1_2_7_8_1 e_1_2_7_7_1 e_1_2_7_19_1 e_1_2_7_18_1 e_1_2_7_17_1 e_1_2_7_16_1 e_1_2_7_2_1 e_1_2_7_15_1 e_1_2_7_14_1 e_1_2_7_13_1 e_1_2_7_12_1 e_1_2_7_11_1 Tellegen P. (e_1_2_7_20_1) 1993; 9 e_1_2_7_10_1 e_1_2_7_21_1 |
References_xml | – volume: 98 start-page: 782 issue: 4 year: 2016 end-page: 788 article-title: Mutations in TBCK, encoding TBC1‐domain‐containing kinase, lead to a recognizable syndrome of intellectual disability and hypotonia publication-title: American Journal of Human Genetics – volume: 2 start-page: e76 issue: 3 year: 2016 article-title: Mutation of TBCK causes a rare recessive developmental disorder publication-title: Neurology Genetics – volume: 32 start-page: 419 issue: 2 year: 2011 end-page: 436 article-title: Prevalence of intellectual disability: A meta‐analysis of population‐based studies publication-title: Research in Developmental Disabilities – volume: 34 start-page: 4845 issue: 37 year: 2015 end-page: 4854 article-title: The landscape and therapeutic relevance of cancer‐associated transcript fusions publication-title: Oncogene – volume: 44 start-page: 1111 issue: 10 year: 2012 end-page: 1116 article-title: Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small‐cell lung cancer publication-title: Nature Genetics – volume: 163 start-page: 712 issue: 3 year: 2015 end-page: 723 article-title: A human interactome in three quantitative dimensions organized by stoichiometries and abundances publication-title: Cell – volume: 9 start-page: e104998 issue: 8 year: 2014 article-title: In‐cell intrabody selection from a diverse human library identifies C12orf4 protein as a new player in rodent mast cell degranulation publication-title: PLoS ONE – volume: 98 start-page: 772 issue: 4 year: 2016 end-page: 781 article-title: Recessive inactivating mutations in TBCK, encoding a Rab GTPase‐activating protein, cause Severe infantile syndromic encephalopathy publication-title: American Journal of Human Genetics – volume: 10 start-page: 148 issue: 2 year: 2015 end-page: 161 article-title: Accelerating novel candidate gene discovery in neurogenetic disorders via whole‐exome sequencing of prescreened multiplex consanguineous families publication-title: Cell Reports – volume: 91 start-page: 100 issue: 1 year: 2017 end-page: 105 article-title: Identification of C12orf4 as a gene for autosomal recessive intellectual disability publication-title: Clinical Genetics – volume: 18 start-page: 62 issue: 1 year: 2017 article-title: Analysis of 31‐year‐old patient with SYNGAP1 gene defect points to importance of variants in broader splice regions and reveals developmental trajectory of SYNGAP1‐associated phenotype: Case report publication-title: BMC Medical Genetics – volume: 9 start-page: 147 issue: 2 year: 1993 end-page: 157 article-title: The construction and validation of a nonverbal test of intelligence: The revision of the Snijders‐Oomen tests publication-title: European Journal of Psychological Assessment – volume: 536 start-page: 285 issue: 7616 year: 2016 end-page: 291 article-title: Analysis of protein‐coding genetic variation in 60,706 humans publication-title: Nature – volume: 30 start-page: 323 issue: 3 year: 2018 end-page: 327 article-title: Genetics of autosomal recessive intellectual disability publication-title: Medizinische Genetik – volume: 21 start-page: 1223 issue: 7 year: 2010 end-page: 1232 article-title: Common genetic variants associate with serum phosphorus concentration publication-title: Journal of the American Society of Nephrology – volume: 23 start-page: 973 issue: 4 year: 2018 end-page: 984 article-title: Mapping autosomal recessive intellectual disability: Combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families publication-title: Molecular Psychiatry – volume: 32 start-page: 139 issue: 3 year: 2016 end-page: 146 article-title: Autism and cancer share risk genes, pathways, and drug targets publication-title: Trends in Genetics – volume: 74 start-page: 293 issue: 3 year: 2017 end-page: 299 article-title: Diagnostic yield and novel candidate genes by exome sequencing in 152 consanguineous families with neurodevelopmental disorders publication-title: JAMA Psychiatry – volume: 24 start-page: 1027 issue: 7 year: 2019 end-page: 1039 article-title: Genetics of intellectual disability in consanguineous families publication-title: Molecular Psychiatry – volume: 21 start-page: 736 issue: 3 year: 2018 end-page: 742 article-title: Autozygome and high throughput confirmation of disease genes candidacy publication-title: Genetics in Medicine – ident: e_1_2_7_2_1 doi: 10.1016/j.celrep.2014.12.015 – ident: e_1_2_7_3_1 doi: 10.1016/j.ajhg.2016.03.016 – ident: e_1_2_7_4_1 doi: 10.1016/j.ajhg.2016.01.016 – ident: e_1_2_7_12_1 doi: 10.1038/nature19057 – ident: e_1_2_7_16_1 doi: 10.1111/cge.12821 – ident: e_1_2_7_14_1 doi: 10.1016/j.ridd.2010.12.018 – ident: e_1_2_7_17_1 doi: 10.1186/s12881-017-0425-4 – volume: 9 start-page: 147 issue: 2 year: 1993 ident: e_1_2_7_20_1 article-title: The construction and validation of a nonverbal test of intelligence: The revision of the Snijders‐Oomen tests publication-title: European Journal of Psychological Assessment contributor: fullname: Tellegen P. – ident: e_1_2_7_9_1 doi: 10.1038/s41380-017-0012-2 – ident: e_1_2_7_15_1 doi: 10.1371/journal.pone.0104998 – ident: e_1_2_7_8_1 doi: 10.1016/j.cell.2015.09.053 – ident: e_1_2_7_11_1 doi: 10.1681/ASN.2009111104 – ident: e_1_2_7_13_1 doi: 10.1038/s41436-018-0138-x – ident: e_1_2_7_7_1 doi: 10.1038/mp.2017.60 – ident: e_1_2_7_5_1 doi: 10.1016/j.tig.2016.01.001 – ident: e_1_2_7_6_1 doi: 10.1212/NXG.0000000000000076 – ident: e_1_2_7_19_1 doi: 10.1038/ng.2405 – ident: e_1_2_7_10_1 doi: 10.1007/s11825-018-0209-z – ident: e_1_2_7_21_1 doi: 10.1038/onc.2014.406 – ident: e_1_2_7_18_1 doi: 10.1001/jamapsychiatry.2016.3798 |
SSID | ssj0000884167 |
Score | 2.146059 |
Snippet | Background
Intellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic... Intellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic variants in a... BackgroundIntellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic... BACKGROUNDIntellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that pathogenic... Abstract Background Intellectual disability (ID) is a feature of many rare diseases caused by thousands of genes. This genetic heterogeneity implies that... |
SourceID | doaj pubmedcentral proquest crossref pubmed wiley |
SourceType | Open Website Open Access Repository Aggregation Database Index Database Publisher |
StartPage | e865 |
SubjectTerms | Adult Age Alleles Armenia - epidemiology Autism C12orf4 Cell growth Child, Preschool Clinical Report Clinical Reports Consanguinity Defects Delineation DNA Mutational Analysis Etiology exome sequencing Facies Genes Genes, Recessive Genotype & phenotype Genotypes Heterogeneity Homozygote Humans Hypotonia Intellectual disabilities intellectual disability Intellectual Disability - diagnosis Intellectual Disability - genetics Intracellular Signaling Peptides and Proteins - genetics Kinases Male Mood Patients Pedigree Phenotype Phenotypes Phenotyping Polymorphism, Single Nucleotide Proteins Signs and symptoms Whole Exome Sequencing |
SummonAdditionalLinks | – databaseName: DOAJ Directory of Open Access Journals dbid: DOA link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lj9MwELbQHhAXxJvAgoyEuIVN_IyPy4rdFVI5sdLeLNuxl0o0QW22Ej-K_8hMnFapAHHh0Ettue7MePyNPfOZkLeBtWC7XJReJ12C92vLJnFVSu4iN1jpabDAefFZXV6JT9fyevbUF-aEZXrgLLgTHXmVQqO4COBInfGmFim2PBjtRfIZGlVsFkyNPrjB6zS9Y5ut2Mnq5oa_b3APme0_I03_n7Dl7ymSc-g67j3nD8j9CTTS0zzZh-RO7B6Ru4vpWvwx-XlKu34bv9EtRL4gKtonelazfp0EXXbUUQh6N3gwCb0h0oeBVphj19F8vIHNablebSigQRqHXMGCg7jbod_0K_htcIyYMLuNdDkrPKHtRNE7_KB4mEuVoniyS1ssc89wFMfBcTGZrMdOT8jV-ccvZ5fl9A5DGSQgvtLDmveJx6CT9NLxmnsQbvRKCXARbRNikM7jix26NTVTEHIZ0JDzLiYVouRPyVHXd_E5oaaWKUbBGHyQyc0bCZiLI-maNpWqCvJmpx37PdNt2EyszCxq0IIGC_IB1bZvR4Ls8QswGzuZjf2X2RTkeKd0O63ajWV461urRmuYx74Z1hteorhRQ2MfiRw_MI9n2Ub2MwHJcAERYUH0gfUcTPWwpVt-HTm9lQbP2jQFeTfa2V__vF1cXOAzrS_-hxBeknuA_6aUuWNyNKxv4yvAWIN_PS6nX8PqKJ8 priority: 102 providerName: Directory of Open Access Journals – databaseName: ProQuest Central dbid: BENPR link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3da9swEBdbCmMvY9_z1hUNxt68xpYlWU-lLf1gkDLGCn0zkiylgcXqYjewP2r_4-5sJU1Yt4e8REK56D70u9PdiZCPNq9BdlmRGullCtavTkvPRMqZdkxhpafCAufJhTi_LL5c8asYcGtjWuXKJvaGug4WY-T7Od7IZaKU8uDmZ4qvRuHtanxC4yHZyTNWliOyc3Ry8fXbOsoCdADikKuus-N8fz6dss8lniUb51Dfrv8-jPl3quQmhO3PoNOn5EkEj_Rw4PYz8sA1z8mjSbwef0F-H9ImLN0PugQPGLaMBk-PszwsfEFnDdUUnN8WA5QwGzx-WGiOuXYNHcIcOOxni3lLARVS1w2VLLiIvu1CG-bw22AgMXF26ehsowCF1rFVb_eLYlCXCkExwktrLHcfYCmug-tiUlnASS_J5enJ9-PzNL7HkFoOyC81oPvGM2el54ZrljEDm-uMEAWYirq0znJt8OUOWassF-B6KVczbbTzwjrOXpFRExr3hlCVce9ckefwwY5uRnHAXgybr0k1FuOEfFhxp7oZ2m5UQ4PlvEIOVsDBhBwh29bj2Ci7_yIsplXUu0o6Nva2FKywcA5rZVRWeCDKKmkKb3RCdldMr6L2ttWdrAEd62HQO7xM0T2H-jkce_0AHa8HGVlTAjvDCvAMEyK3pGeL1O2RZnbd9_YWEixsWSbkUy9n__zz1eTsDJ9rfft_-t-Rx4DwYlLcLhl1i1v3HlBUZ_aiqvwBxYMgow priority: 102 providerName: ProQuest – databaseName: Scholars Portal Open Access Journals dbid: M48 link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1Lb9QwELZKkRAXVJ4NFGQkxC1lE7_iQ4VK1YeQlhMr9RbZib2s1E0gya7oj-I_MuMkq121SBxyWXudycx4PLZnviHkQ5GWoLuMx1Z5FYP1K-PMMxkLZhzTmOmpMcF5-k1ezfjXa3G9R8ZqmwMD23u3dlhPatbcHP_-dfsZJvzJACD6aTmfs-NMigfkYQrrIQZ2TQcnP9jjDK_WVKgyl_JYp1KPKLRbf95ZlwJ8_30-593QyW2XNqxJFwfkyeBM0tNe-k_JnquekUfT4br8OflzSqt67W7oGnbEwEJae3qWpHXjOV1U1FDYDLd4YAm961ULAy0x9q6i_bEHNvtFs2wpeInUdX1mCw5iVl3d1kt4NxhMDKRdO7rYSkih5QDd291SPOSlUlI88aUlpr_3biqOg-NikFmNnV6Q2cX597OreKjPEBcCPMHYgi2wnrlCeWGFYQmzwGhnpeRgOsqscIUwFit5qFInwHYhtSuZscZ5WTjBXpL9qq7cIaE6Ed45nqbwIMKb1QJ8MYZgbEpP5CQi70fp5D97GI68B1xOc5RgDhKMyBcU26YdgbPDD3Uzz4d5mCvHJr7IJOMFrMtGW51wD0QVWlnurYnI0Sj0fFTGPMXb4ERmSgEdm2aYh3i5YoKEQh-B2D9Ax6teRzaUAGcYh51iRNSO9uyQuttSLX4ErG-pwOJmWUQ-Bj3758fn08tLLN_6-n87viGPwfcbwuWOyH7XrNxb8K86-y5Mn79d6CU- priority: 102 providerName: Scholars Portal – databaseName: Wiley Online Library Open Access dbid: 24P link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1Lb9QwELagSIgLojxDW2QkxC1042d8LBVthbSIA5V6i2zHXlbqJmiTrsSP4j92xsmGrgCJw17WXu_E45l8Hs98JuSdZzWsXS5yp6POwfvVeRm5yiW3gRus9DRY4Dz_oi4uxecreTVmVWItzMAPMQXc0DKSv0YDt647_k0aulos-IdSyfvkAaAahbcXMPF1iq-ABIA1dLpbjoncMGW23LMzdrz98c7bKJH2_w1p_pkweRfIpjfR2RPyeISQ9GTQ-T65F5qn5OF8PCR_Rn6d0KbdhGu6gX0wTBxtIz0tWLuOgi4bailsgTsMU0Jv2PfDQCvMuGvoEOzA5rhcrzoK2JCGfqhnwUHsTd927Qr-G9wkps9uAl3eKUOh9UjY2_-kGNqlSlGM89Iai94HcIrj4LiYWtZip-fk8uzTt9OLfLyVIfcS8F_uwAO4yIPXUTppecEdTHRwSglwGHXpg5fW4f0dujYFTLtUJtTcOhui8kHyF2SvaZvwilBTyBiCYAw-yOvmjAQExpGCTZuZmmXk7VY71Y-BfKMaaJZZhRqsQIMZ-Yhqm9qRLjt90a4X1Wh9lQ58Fn2puPDwNrbGmUJEEMob7UR0NiOHW6VXow13FcMz4EKVWoMcUzNYHx6p2KSh1Eci4w_I8XJYI5MkMDNcwP4wI3pn9eyIutvSLL8nhm-lwc-WZUbep3X2z4ev5ufneGnr6__teEAeAeIbk-QOyV6_vglHgKp69yaZzy1SPiCH priority: 102 providerName: Wiley-Blackwell |
Title | A novel variant of C12orf4 in a consanguineous Armenian family confirms the etiology of autosomal recessive intellectual disability type 66 with delineation of the phenotype |
URI | https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fmgg3.865 https://www.ncbi.nlm.nih.gov/pubmed/31334606 https://www.proquest.com/docview/2287016877 https://search.proquest.com/docview/2287530825 https://pubmed.ncbi.nlm.nih.gov/PMC6732288 https://doaj.org/article/7e30fc8634c847a9b914fed3c97b4fba |
Volume | 7 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Li9swEBabLZReSt_rdhtUKL05D-tlH3fDPih4CaULezOWLKWGtb0k3kB_VP9jZ2Q7JLS99OAcLCFPNCNpZjTzDSGfTVSA7DIeauVUCLtfEcaOyVCw3LIEMz0TTHBOb-T1Lf96J-6OiBhyYXzQvtHlpL6vJnX5w8dWPlRmOsSJTZfpQioQQ7DcRmQEx--eie633xhv0tQANDuLptVqxSaxxCI1DEwyLrG80d4p5MH6_6Zh_hkoua_A-hPo8gV53quO9Kwj8SU5svUr8jTtL8dfk19ntG629p5uwf6FCaONo4t51Kwdp2VNcwqm7wbdk9Ab7H0YqMJIu5p2Tg5sduW62lDQCaltuzwWHCR_bJtNU8G3YXvEsNmtpeVe-gkteqDe9idFly6VkqJ_lxaY7N4ppTgOjoshZQ12ekNuLy--L67DvhpDaATofaGGla8ds0Y5oUUOM6lhnq2WksNGUcTGGpFrrNuhimQeSTC8EluwXOfWSWMFe0uO66a2J4Qmc-Gs5VEED-K56USA5sUQek0lMzkLyKeBO9lDB7qRdfDKUYbMzICZATlHtu3aESbbv2jWq6wXlkxZNnMmlowbOIXzRCdz7oAokyjNnc4DcjowPevX7iaL8O53LmOlgI5dM6w6vErJPYd8H4FIP0DHu05GdpQMMhYQdSA9B6QetoCge2TvXrAD8sXL2T__fJZeXWGx1vf__YkP5Bmofn203Ck5bteP9iOoV60ek1HEl2Py5PziZvlt7J0U8JvyeOwX2m-48Sxp |
link.rule.ids | 230,314,727,780,784,864,885,2102,11562,21388,24318,27924,27925,33744,33745,43805,46052,46476,50814,50923,53791,53793,74302 |
linkProvider | National Library of Medicine |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3db9MwELegk2AviG8CA4yEeAtr4tiOn9A2bSuwVght0t6s2LFLJZpsTVaJP4r_kbvELa34eOhLbblX34fvznc_E_LWpiXILstiI72MwfqVce6ZiDkrHFPY6amwwXk8EaOL7NMlvwwJtyaUVa5sYmeoy9pijnw_xRu5RORSfri6jvHVKLxdDU9o3CY7iJzOB2Tn8Hjy5es6ywJ0gMchV6izw3R_Pp2y9zmeJRvnUAfX_zcf889SyU0XtjuDTu6Te8F5pAc9tx-QW656SO6Mw_X4I_LzgFb10n2nS4iAYcto7elRktYLn9FZRQsKwW-DCUqYDRE_LDTHWruK9mkOHPazxbyh4BVS1_adLLhIcdPWTT2H3wYDiYWzS0dnGw0otAxQve0PikldKgTFDC8tsd29d0txHVwXi8pqnPSYXJwcnx-N4vAeQ2w5eH6xAd03njkrPTe8YAkzsLnOCJGBqShz6ywvDL7cIUuVpAJCL-VKVpjCeWEdZ0_IoKor94xQlXDvXJam8EFEN6M4-F4MwdekGophRN6suKOvetgN3QMspxo5qIGDETlEtq3HESi7-6JeTHXQOy0dG3qbC5ZZOIcLZVSSeSDKKmkyb4qI7K2YroP2Nvq3rAEd62HQO7xMKToOdXM4Yv0AHU97GVlTAjvDMogMIyK3pGeL1O2Ravatw_YWEixsnkfkXSdn__zzenx6is-1Pv8__a_J3dH5-EyffZx8fkF2wdsLBXJ7ZNAubtxL8Kha8yqozS9l1yOL |
linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfR3bbtMw1IJOmnhB3AkMMBLiLbSJYzt-QttYNy6tJsSkvVmxY5dKNBlNVomP4h85J3FLKy4Pfakt99TnfnwuhLyyaQm0y7LYSC9jkH5lnHsmYs4KxxRWeioscJ5MxdlF9uGSX4b8pyakVa5lYieoy9pijHyY4otcInIphz6kRZy_G7-9-h7jBCl8aQ3jNG6SPdCKo3RA9o5OpuefNxEXgAmsD7nuQDtKh4vZjL3JUa9s6aSudf_f7M0_0ya3zdlOH43vkNvBkKSHPebvkhuuukf2J-Gp_D75eUireuW-0RV4w3B9tPb0OEnrpc_ovKIFBUe4wWAl7AbvHw5aYN5dRfuQBy77-XLRULAQqWv7qhY8pLhu66ZewG-DsMQk2pWj861iFFqGtr3tD4oBXioExWgvLbH0vTdR8Rw8FxPMatz0gFyMT74cn8VhNkNsOViBsQE5YDxzVnpueMESZuBynREiA7FR5tZZXhic4iFLlaQC3DDlSlaYwnlhHWcPyaCqK_eYUJVw71yWpvDB7m5GcbDDGDZik2okRhF5ucaOvupbcOi-2XKqEYMaMBiRI0TbZh2bZndf1MuZDjyopWMjb3PBMgs6uVBGJZkHoKySJvOmiMjBGuk6cHKjf9MdwLFZBh7Eh5Wiw1C3h2PfH4DjUU8jG0jgZlgGXmJE5A717IC6u1LNv3Z9voUEaZvnEXnd0dk__7yenJ7i6NYn_4f_BdkHjtGf3k8_PiW3wPALuXIHZNAur90zMK5a8zxwzS_QIie4 |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+novel+variant+of+C12orf4+in+a+consanguineous+Armenian+family+confirms+the+etiology+of+autosomal+recessive+intellectual+disability+type+66+with+delineation+of+the+phenotype&rft.jtitle=Molecular+genetics+%26+genomic+medicine&rft.au=Hancarova%2C+Miroslava&rft.au=Babikyan%2C+Davit&rft.au=Bendova%2C+Sarka&rft.au=Midyan%2C+Susanna&rft.date=2019-09-01&rft.issn=2324-9269&rft.eissn=2324-9269&rft.volume=7&rft.issue=9&rft.epage=n%2Fa&rft_id=info:doi/10.1002%2Fmgg3.865&rft.externalDBID=10.1002%252Fmgg3.865&rft.externalDocID=MGG3865 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2324-9269&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2324-9269&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2324-9269&client=summon |