title: Novel splice-site mutation in WDR62 revealed by whole-exome sequencing in a Sudanese family with primary microcephaly.
abstract: The WDR62 gene encodes a scaffold protein of the c-Jun N-terminal kinase (JNK) pathway. It plays a critical role in laying out various cellular layers in the cerebral cortex during embryogenesis, and hence the dramatic clinical features resulting from WDR62 mutations. These mutations are associated with autosomal recessive primary microcephaly 2, with or without cortical malformations (MCPH2). Using whole exome sequencing we uncovered a novel WDR62 variant; c.390G > A, from two Sudanese siblings whose parents are first cousins. The patients suffered MCPH2 with incomplete lissencephaly and developmental delay. The mutation affects the last nucleotide of exon4, and probably leads to aberrant splicing, which may result in a truncated protein lacking all functional domains.
authors.affiliation: Pediatric Department, Dubai Health Authority, Latifa Hospital, Dubai, United Arab Emirates.
authors.forename: Fatma
authors.initials: F
authors.lastname: Bastaki
authors.affiliation: Pediatric Department, Dubai Health Authority, Latifa Hospital, Dubai, United Arab Emirates.
authors.forename: Madiha
authors.initials: M
authors.lastname: Mohamed
authors.affiliation: Centre for Arab Genomic Studies, Dubai, United Arab Emirates.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Nair
authors.affiliation: Pediatric Department, Dubai Health Authority, Latifa Hospital, Dubai, United Arab Emirates.
authors.forename: Fatima
authors.initials: F
authors.lastname: Saif
authors.affiliation: Pediatric Department, Dubai Health Authority, Latifa Hospital, Dubai, United Arab Emirates.
authors.forename: Nafisa
authors.initials: N
authors.lastname: Tawfiq
authors.affiliation: Pediatric Department, Dubai Health Authority, Latifa Hospital, Dubai, United Arab Emirates.
authors.forename: Gururaj
authors.initials: G
authors.lastname: Aithala
authors.affiliation: Pediatric Department, Dubai Health Authority, Latifa Hospital, Dubai, United Arab Emirates.
authors.forename: Majdi
authors.initials: M
authors.lastname: El-Halik
authors.affiliation: Centre for Arab Genomic Studies, Dubai, United Arab Emirates.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al-Ali
authors.affiliation: Centre for Arab Genomic Studies, Dubai, United Arab Emirates.
authors.forename: Abdul Rezzak
authors.initials: AR
authors.lastname: Hamzeh
mesh_terms: D001921:Brain / Q000473:pathology; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D059472:Exome; D017809:Fatal Outcome; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008831:Microcephaly / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites; D013397:Sudan
chemical_list: D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D022821:RNA Splice Sites; C552527:WDR62 protein, human
keywords: Sudanese; WDR62; aberrant splicing; consanguinity; primary microcephaly 2