Novel mutation in Sjogren-Larsson syndrome is associated with divergent neurologic phenotypes
Sjögren-Larsson syndrome is an inherited disorder of lipid metabolism caused by mutations in the ALDH3A2 gene that codes for fatty aldehyde dehydrogenase, which results in accumulation of fatty aldehydes and alcohols and is characterized by ichthyosis, intellectual disability, and spastic diplegia/q...
Saved in:
Published in | Journal of child neurology Vol. 28; no. 10; p. 1259 |
---|---|
Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.10.2013
|
Subjects | |
Online Access | Get more information |
Cover
Loading…
Abstract | Sjögren-Larsson syndrome is an inherited disorder of lipid metabolism caused by mutations in the ALDH3A2 gene that codes for fatty aldehyde dehydrogenase, which results in accumulation of fatty aldehydes and alcohols and is characterized by ichthyosis, intellectual disability, and spastic diplegia/quadriplegia. The authors describe 2 unrelated Honduran patients who carried the same novel homozygous nonsense mutation (c.1309A>T, p.K437X) and ALDH3A2 DNA haplotype, but widely differed in disease severity. One patient exhibited spastic quadriplegia with unusual neuroregression, whereas the other patient had the usual static form of spastic diplegia with neurodevelopmental disabilities. Biochemical analyses showed a similar profound deficiency of fatty aldehyde dehydrogenase activity and impaired fatty alcohol metabolism in both patients' cultured fibroblasts. These results indicate that variation in the neurologic phenotype of Sjögren-Larsson syndrome is not strictly determined by the ALDH3A2 mutation or the biochemical defect as expressed in cultured fibroblasts, but by unidentified epigenetic/environmental factors, gene modifiers, or other mechanisms. |
---|---|
AbstractList | Sjögren-Larsson syndrome is an inherited disorder of lipid metabolism caused by mutations in the ALDH3A2 gene that codes for fatty aldehyde dehydrogenase, which results in accumulation of fatty aldehydes and alcohols and is characterized by ichthyosis, intellectual disability, and spastic diplegia/quadriplegia. The authors describe 2 unrelated Honduran patients who carried the same novel homozygous nonsense mutation (c.1309A>T, p.K437X) and ALDH3A2 DNA haplotype, but widely differed in disease severity. One patient exhibited spastic quadriplegia with unusual neuroregression, whereas the other patient had the usual static form of spastic diplegia with neurodevelopmental disabilities. Biochemical analyses showed a similar profound deficiency of fatty aldehyde dehydrogenase activity and impaired fatty alcohol metabolism in both patients' cultured fibroblasts. These results indicate that variation in the neurologic phenotype of Sjögren-Larsson syndrome is not strictly determined by the ALDH3A2 mutation or the biochemical defect as expressed in cultured fibroblasts, but by unidentified epigenetic/environmental factors, gene modifiers, or other mechanisms. |
Author | Matheus, M Gisele Rizzo, William B Davis, Kathleen Amador, Claudia S'Aulis, Dana Holden, Kenton R |
Author_xml | – sequence: 1 givenname: Kathleen surname: Davis fullname: Davis, Kathleen organization: 1Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA – sequence: 2 givenname: Kenton R surname: Holden fullname: Holden, Kenton R – sequence: 3 givenname: Dana surname: S'Aulis fullname: S'Aulis, Dana – sequence: 4 givenname: Claudia surname: Amador fullname: Amador, Claudia – sequence: 5 givenname: M Gisele surname: Matheus fullname: Matheus, M Gisele – sequence: 6 givenname: William B surname: Rizzo fullname: Rizzo, William B |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23034980$$D View this record in MEDLINE/PubMed |
BookMark | eNo1j81KAzEURoMo9kf3riQvMHqTTCaZpRStQtGFupSSZG7blE4yJGmlb29BXR04cD74JuQ8xICE3DC4Y0ype9BagBKa8boBqdkZGTMFutJcixGZ5LwFAC1buCQjLkDUrYYx-XqNB9zRfl9M8TFQH-j7Nq4ThmphUs4nlY-hS7FH6jM1J-O8KdjRb182tPMHTGsMhQbcp7iLa-_osMEQy3HAfEUuVmaX8fqPU_L59Pgxe64Wb_OX2cOicnWjSmWVtUyg4wKlFcZobvlKtsKA1dqtVFOjVFw6cKaVQnDbNNwJe2pbpXjd8Sm5_d0d9rbHbjkk35t0XP7_5D-GqVaT |
CitedBy_id | crossref_primary_10_1007_s40278_013_6945_6 crossref_primary_10_1111_pan_14034 crossref_primary_10_1517_21678707_2016_1154453 crossref_primary_10_1177_08830738211029390 crossref_primary_10_1002_mgg3_947 crossref_primary_10_1002_jmd2_12099 crossref_primary_10_1016_j_ejmg_2017_11_006 crossref_primary_10_1186_s12881_018_0663_0 crossref_primary_10_1038_s10038_019_0637_x crossref_primary_10_1111_cge_13058 crossref_primary_10_1038_ncomms5439 crossref_primary_10_1515_jpm_2017_0187 crossref_primary_10_1007_s00403_019_01953_6 crossref_primary_10_1002_humu_23679 |
ContentType | Journal Article |
DBID | CGR CUY CVF ECM EIF NPM |
DOI | 10.1177/0883073812460581 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) |
DatabaseTitleList | MEDLINE |
Database_xml | – sequence: 1 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: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | no_fulltext_linktorsrc |
Discipline | Medicine |
EISSN | 1708-8283 |
ExternalDocumentID | 23034980 |
Genre | Journal Article Case Reports Research Support, N.I.H., Extramural |
GrantInformation_xml | – fundername: NIAMS NIH HHS grantid: R01 AR044552 |
GroupedDBID | --- -TM .2E .2F .2G .2J .2N .GJ 0-V 01A 0R~ 18M 1~K 29K 31R 31S 31U 31X 31Y 31Z 36B 39C 3V. 4.4 53G 54M 5GY 5RE 5VS 7X7 88E 8A4 8FI 8FJ 8FQ 8R4 8R5 AABMB AABOD AACKU AACMV AACTG AADTT AADUE AAEWN AAGGD AAGMC AAJIQ AAJOX AAJPV AAKGS AAMGE AANSI AAPEO AAQDB AAQQG AAQQT AAQXH AARDL AARIX AATAA AATBZ AAUAS AAXOT AAYTG AAZBJ ABAWP ABCCA ABDWY ABEIX ABFWQ ABHKI ABHQH ABIVO ABJIS ABJNI ABKRH ABLUO ABNCE ABPGX ABPNF ABPPZ ABQKF ABQXT ABRHV ABUWG ABVFX ABVVC ABYTW ACAEH ACARO ACDSZ ACDXX ACFEJ ACFMA ACFYK ACGBL ACGFO ACGFS ACGZU ACJER ACJTF ACLFY ACLHI ACLZU ACNXM ACOFE ACOXC ACROE ACSBE ACSIQ ACTQU ACUAV ACUIR ACXKE ACXMB ACZ ADBBV ADEIA ADMPF ADNBR ADRRZ ADTBJ ADUKL ADZZY AECGH AECVZ AEDTQ AEKYL AENEX AEPTA AEQLS AERKM AESZF AEUHG AEUIJ AEWDL AEWHI AEXFG AEXNY AFEET AFKBI AFKRA AFKRG AFMOU AFQAA AFUIA AFVCE AGKLV AGNHF AGWFA AGWNL AHHFK AHMBA AIGRN AIKWM AIOMO AJABX AJEFB AJMMQ AJSCY AJUZI AJXAJ AJXGE ALIPV ALKWR ALMA_UNASSIGNED_HOLDINGS ALSLI ALTZF AMCVQ ANDLU ARALO ARTOV ASPBG AUTPY AUVAJ AVWKF AYAKG AZFZN AZQEC B3H B8M B8O B8R B8Z B93 B94 BBRGL BCR BDDNI BENPR BKIIM BKNYI BKSCU BLC BPACV BPHCQ BSEHC BVXVI BWJAD BYIEH C45 CAG CBRKF CCPQU CDWPY CFDXU CGR CJNVE COF CORYS CQQTX CS3 CUTAK CUY CVF D-I DB0 DC- DC. DC0 DD- DD0 DE- DF0 DO- DOPDO DU5 DV7 DWQXO D~Y EBS ECM EIF EJD EMOBN ESX F5P FEDTE FHBDP FYUFA GNUQQ GROUPED_SAGE_PREMIER_JOURNAL_COLLECTION H13 HF~ HMCUK HVGLF HZ~ J8X JCYGO K.F K.J K9- L7B M0P M0R M1P M2M M3G M4V N9A NPM O9- OVD P.B P2P PQEDU PQQKQ PROAC PSQYO PSYQQ Q1R Q2X Q7K Q7L Q7R Q7U Q7X Q82 Q83 ROL RWL RXW S01 SCNPE SDB SFB SFC SFK SFN SGA SGO SGP SGR SGV SGX SGZ SHG SNB SPQ SPV SQCSI STM TAE TEORI UKHRP WH7 ZGI ZONMY ZPPRI ZRKOI ZSSAH ZXP |
ID | FETCH-LOGICAL-c467t-b7bb13ec23e5b3aa82b2f593a0b88cf764e5725c0ca95332b662c3b46797724d2 |
IngestDate | Wed Oct 16 00:46:42 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 10 |
Keywords | phenotype mutation aldehyde dehydrogenase fatty alcohol Sjögren-Larsson spasticity ichthyosis neurologic |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c467t-b7bb13ec23e5b3aa82b2f593a0b88cf764e5725c0ca95332b662c3b46797724d2 |
OpenAccessLink | https://europepmc.org/articles/pmc6028016?pdf=render |
PMID | 23034980 |
ParticipantIDs | pubmed_primary_23034980 |
PublicationCentury | 2000 |
PublicationDate | 2013-10-01 |
PublicationDateYYYYMMDD | 2013-10-01 |
PublicationDate_xml | – month: 10 year: 2013 text: 2013-10-01 day: 01 |
PublicationDecade | 2010 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | Journal of child neurology |
PublicationTitleAlternate | J Child Neurol |
PublicationYear | 2013 |
SSID | ssj0008590 |
Score | 2.1813285 |
Snippet | Sjögren-Larsson syndrome is an inherited disorder of lipid metabolism caused by mutations in the ALDH3A2 gene that codes for fatty aldehyde dehydrogenase,... |
SourceID | pubmed |
SourceType | Index Database |
StartPage | 1259 |
SubjectTerms | Aldehyde Oxidoreductases - genetics Aldehyde Oxidoreductases - metabolism Child, Preschool Female Fibroblasts - metabolism Humans Ichthyosis - genetics Ichthyosis - metabolism Lipid Metabolism - genetics Male Mutation Phenotype Severity of Illness Index Sjogren-Larsson Syndrome - genetics Sjogren-Larsson Syndrome - metabolism |
Title | Novel mutation in Sjogren-Larsson syndrome is associated with divergent neurologic phenotypes |
URI | https://www.ncbi.nlm.nih.gov/pubmed/23034980 |
Volume | 28 |
hasFullText | |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LS8NAEF6qgngR32_Zg55KNNnNJptjEUVEe9FCL1J2N1uotIlg68G_4J92Jm-KFfUSQrYbSr5vZ2dm50HImW9DO4Sd0jE64I5vBXOwUJETe1oDKCbiPuY7P3SD255_1xf9VuuzEbU0m-oL8_FtXsl_UIVngCtmyf4B2eql8ADuAV-4AsJw_RXG3fTdjtuTWRExOIKl-pKCAZ0492CvYm_BsiAB9i1XBRJlwHmMIRmYWdXOilpmQrCNIV8p-mXfFqitWfZ3NaNyyFfVCsrwjIov6bgQbSDTsYZHdbT0eM7CTtmPHdhXbRCdiYpzL8LVWM3ikWq6Jrw6yA12llychq7ERHXelLdMNnnlNqQnKFvR92I9O1gGgYgSCVUSPMz1mj8FYF4nGcxgU3E_yttD_Tw6V2i7HFoiS6FEYdlFx0-xqUsRufUp9-X8X8Ga0sX0Ofsk01OeNsh6gRTt5GzZJC2bbJHVhyKEYps8Z6ShJWnoKKFzpKElaejojdakoUgaWpGG1qShNWl2SO_m-unq1il6bDgGtsipo0OtPW4N41ZorpRkmg1FxJWrpTTDMIDlGzJhXKMwEJnpIGCGa5gLhgPzY7ZLlpM0sfuEejq0EuxxYbTwYxNJJQSo366NQUcGM_eA7OUfZvCaF1IZlJ_scOHIEVmriXVMVoawcu0JqIFTfZoB9AVetF4j |
link.rule.ids | 786 |
linkProvider | National Library of Medicine |
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=Novel+mutation+in+Sjogren-Larsson+syndrome+is+associated+with+divergent+neurologic+phenotypes&rft.jtitle=Journal+of+child+neurology&rft.au=Davis%2C+Kathleen&rft.au=Holden%2C+Kenton+R&rft.au=S%27Aulis%2C+Dana&rft.au=Amador%2C+Claudia&rft.date=2013-10-01&rft.eissn=1708-8283&rft.volume=28&rft.issue=10&rft.spage=1259&rft_id=info:doi/10.1177%2F0883073812460581&rft_id=info%3Apmid%2F23034980&rft_id=info%3Apmid%2F23034980&rft.externalDocID=23034980 |