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

Autor: Alrayes N; Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Cell Sciences and Genetics Research Centre, St. George's University of London (SGUL), London SW17 0RE, United Kingdom., Mohamoud HS; Cell Sciences and Genetics Research Centre, St. George's University of London (SGUL), London SW17 0RE, United Kingdom., Ahmed S; Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Genetic Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia., Almramhi MM; Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia., Shuaib TM; Department of Paediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia., Wang J; Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; BGI-Shenzhen, Shenzhen 518083, China., Al-Aama JY; Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia., Everett K; Cell Sciences and Genetics Research Centre, St. George's University of London (SGUL), London SW17 0RE, United Kingdom., Nasir J; Cell Sciences and Genetics Research Centre, St. George's University of London (SGUL), London SW17 0RE, United Kingdom., Jelani M; Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia; Medical Genetics and Molecular Biology Unit, Biochemistry Department, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan. Electronic address: mjelani@kau.edu.sa.
Jazyk: angličtina
Zdroj: Journal of the neurological sciences [J Neurol Sci] 2016 Apr 15; Vol. 363, pp. 240-4. Date of Electronic Publication: 2016 Mar 02.
DOI: 10.1016/j.jns.2016.02.063
Abstrakt: 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.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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