title: Molecular analysis of 23 Pakistani families with autosomal recessive primary microcephaly using targeted next-generation sequencing.
abstract: Primary microcephaly is genetically heterogeneous, with most cases showing autosomal recessive inheritance. We designed a panel containing 46 primary microcephaly-causing genes and performed mutation screening in 23 Pakistani families with autosomal recessive primary microcephaly. We found mutations that were pathogenic or likely to be pathogenic in 22 families, including 18 families with known mutations in ASPM, three with novel mutations in WDR62 and one with a novel in-frame deletion mutation in CASC5. Affected individuals harbored the c.3978G>A (p.W1326*) ASPM mutation in 15 families (nine consanguineous and six non-consanguineous), suggesting a high carrier rate of the nonsense mutation in Pakistani individuals. We identified three novel homozygous WDR62 mutations, including an intragenic deletion of 10 299 bp, a splicing mutation and a nonsense mutation. Our results confirm that mutations in ASPM or WDR62 are the major cause of autosomal recessive primary microcephaly in the Pakistani population.
authors: McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
authors: Rongrong
authors: R
authors: Wang
authors: The Research Center for Medical Genomics, China Medical University, Shenyang, China.
authors: Amjad
authors: A
authors: Khan
authors: The Research Center for Medical Genomics, China Medical University, Shenyang, China.
authors: Shirui
authors: S
authors: Han
authors: McKusick-Zhang Center for Genetic Medicine, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
authors: Xue
authors: X
authors: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D005190:Family; D018740:Genetic Heterogeneity; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010154:Pakistan; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C467202:ASPM protein, human; D018797:Cell Cycle Proteins; C472643:Knl1 protein, human; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C552527:WDR62 protein, human