A novel WDR62 mutation causes primary microcephaly in a Pakistani family

• Published in: Molecular biology reports Vol. 40; no. 1; pp. 591 - 595
• Main Authors: Memon, Mazhar Mustafa, Raza, Syed Irfan, Basit, Sulman, Kousar, Rizwana, Ahmad, Wasim, Ansar, Muhammad
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 2013; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Base Sequence; Biomedical and Life Sciences; Brain - pathology; Consanguinity; Developmental disabilities; Female; Genetic disorders; Genetic markers; Genotype; Histology; Humans; Life Sciences; Male; Microcephaly - diagnosis; Microcephaly - genetics; Morphology; Mutagenesis; Mutation; Nerve Tissue Proteins - genetics; Neuroimaging; Pakistan; Pedigree; Tomography, X-Ray Computed; Pakistan; MCPH; Pakistan; Mutation; Microcephaly; Head circumference
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-012-2097-7

Autosomal recessive primary microcephaly (MCPH) is a heterogeneous disorder which mainly affects neurodevelopment. Generally, MCPH patients exhibit mild brain structural anomalies and simplified cerebral cortex, but few recently identified genes are associated with severe brain malformations. Here, we report a five generation Pakistani family with three affected individuals presenting primary microcephaly, intellectual disability, schizencephaly and hypoplasia of corpus callosum. The comparison of available clinical information led to candidate gene mapping and sequencing of WD repeat domain 62 ( WDR62 ) gene which is mostly associated with severe brain malformations. A homozygous deletion mutation c.1143delA was detected in exon 9 of WDR62 gene, in all affected individuals, which resulted in frameshift and protein truncation (p.H381PfsX48). This study supports the frequent involvement of WDR62 in patients with gross brain malformations.