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.
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Acknowledgements
We thank all the individuals for their participation in this study. This work was financially supported by the National Natural Science Foundation of China (NSFC) (grant number: 81230015), the Beijing Municipal Science and Technology Commission (grant number: Z151100003915078) and National Key Research and Development Program (grant number: 2016YFC1000504). We thank Prof. Mario Tosi from Rouen Institute for Biomedical Research (France) for providing the pCAS2 plasmid.
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Wang, R., Khan, A., Han, S. et al. Molecular analysis of 23 Pakistani families with autosomal recessive primary microcephaly using targeted next-generation sequencing. J Hum Genet 62, 299–304 (2017). https://doi.org/10.1038/jhg.2016.128
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DOI: https://doi.org/10.1038/jhg.2016.128
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