Journal
JOURNAL OF THE NEUROLOGICAL SCIENCES
Volume 363, Issue -, Pages 240-244Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jns.2016.02.063
Keywords
Autosomal recessive primary microcephaly; Alkylglycerol monooxygenase; Whole exome sequencing; Novel homozygous; Frameshift deletion mutation; Saudi Arabia
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Funding
- Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah [1-287/1433/HiCi]
- DSR
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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 100x 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.G1u324Lysfs12*) 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. (C) 2016 Elsevier B.V. All rights reserved.
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