A novel single base pair duplication in WDR62 causes primary microcephaly

• Published in: BMC genetics Vol. 15; no. 1; p. 107
• Main Authors: Rupp, Verena, Rauf, Sobiah, Naveed, Ishrat, Windpassinger, Christian, Mir, Asif
• Format: Journal Article
• Language: English
• Published: England BioMed Central 11-10-2014
• Subjects: Adult; Amino Acid Sequence; Animals; Cell cycle; Cell division; Child, Preschool; Chromosomes, Human, Pair 19; Gene Duplication; Genes; Genotype; Humans; Kinases; Localization; Male; Microcephaly; Microcephaly - genetics; Microcephaly - pathology; Molecular Sequence Data; Mutation; Nerve Tissue Proteins - genetics; Patients; Pedigree; Proteins; Sequence Alignment; Sequence Analysis, DNA
• ISSN: 1471-2156; 1471-2350; 1471-2156
• DOI: 10.1186/s12881-014-0107-4

Primary microcephaly is a disorder of the brain resulting in a reduced head circumference that can come along with intellectual disability but with hardly any other neurological abnormalities.
In this study we report on three Pakistani males from a consanguineous family with 2, 4 and 25 years, diagnosed with autosomal recessive primary microcephaly. By genotyping, Sanger sequencing and using bioinformatical approaches the disease causing mutation was identified and evaluated.
By using a 250K SNP array, we were able to detect an 11Mb large autozygous region in the MCPH2 locus on chromosome 19q13.12. Sequencing of the associated gene, WDR62, revealed the frameshift causing single base pair duplication, c.2527dupG. This mutation is predicted to affect the structural features of WDR62 which in turn changes the conformation and function of the protein. Aspartic acid (D) at position 843 was found to be conserved among various ortholog species. The present findings will be helpful in genetic diagnosis of patients and future studies of WDR62.