The alkylglycerol monooxygenase ( AGMO ) gene previously involved in autism also causes a novel syndromic form of primary microcephaly in a consanguineous Saudi family

• Published in: Journal of the neurological sciences Vol. 363; pp. 240 - 244
• Main Authors: Alrayes, Nuha, Mohamoud, Hussein Sheikh Ali, Ahmed, Saleem, Almramhi, Mona Mohammad, Shuaib, Taghreed Mohammad, Wang, Jun, Al-Aama, Jumana Yousuf, Everett, Kate, Nasir, Jamal, Jelani, Musharraf
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2016
• Subjects: Alkylglycerol monooxygenase; Amino Acid Sequence; Autistic Disorder - genetics; Autosomal recessive primary microcephaly; Base Sequence; Child; Consanguinity; Frameshift deletion mutation; Humans; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Male; Microcephaly - diagnosis; Microcephaly - genetics; Mixed Function Oxygenases - genetics; Neurology; Novel homozygous; Pedigree; Saudi Arabia; Whole exome sequencing; Saudi Arabia; Autosomal recessive primary microcephaly; Novel homozygous; Alkylglycerol monooxygenase; Whole exome sequencing; Frameshift deletion mutation
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2016.02.063

Abstract Autosomal recessive primary microcephaly (MCPH) refers to a genetically heterogeneous group of neurodevelopmental disorders in which patients exhibit a marked decrease in occipitofrontal head circumference at birth and a variable degree of intellectual disability. To date, 18 genes have been reported for MCPH worldwide. We enrolled a consanguineous family from Saudi Arabia presenting with primary microcephaly, developmental delay, short stature and intellectual disability. Whole exome sequencing (WES) with 100 × coverage was performed on two affected siblings after defining common regions of homozygosity through genome-wide single nucleotide polymorphism (SNP) microarray genotyping. WES data analysis, confirmed by subsequent Sanger sequence validation, identified a novel homozygous deletion mutation (c.967delA; p.Glu324Lysfs12*) in exon 10 of the alkylglycerol monooxygenase ( AGMO ) gene on chromosome 7p21.2. Population screening of 178 ethnically matched control chromosomes and consultation of the Exome Aggregation Consortium database, containing 60,706 individuals' exomes worldwide, confirmed that this mutation was not present outside the family. To the best of our knowledge, this is the first evidence of an AGMO mutation underlying primary microcephaly and intellectual disability in humans. Our findings further expand the genetic heterogeneity of MCPH in familial cases.