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      https://www.ias.ac.in/article/fulltext/jgen/096/02/0383-0387

    • Keywords

       

      primary microcephaly; Pakistani families; exome sequencing; ASPM gene; armadillo-type fold.

    • Abstract

       

      Autosomal recessive primary microcephaly is a rare genetic disorder that is characterized by reduced head circumference and a varying degree of intellectual disability. Genetic studies on consanguineous families with primary microcephaly have identified 15 (MCPH) causative genes that include MCPH1, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135,CEP152, ZNF335, PHC1, CDK6, CENPE, SASS6 MFSD2A ANKLE2 and CIT (Khan et al. 2014; Yamamoto et al. 2014; Alakbarzade et al. 2015;Morris-Rosendahl and Kaindl 2015; Basit et al. 2016). Physiologically, most of these MCPH proteins are involved in cell cycle and its regulation. In the present clinical genetic study, we have present two consanguineous Pakistanifamilies segregating primary microcephaly and intellectual disability. These families were ascertained from the Saraiki ethnic part of Khyber-Pakhtunkhwa province in Pakistan. Whole exome sequencing in one family revealed a novel 1-bp deletion NM_018136.4: c.10013delA (p.Asp3338Valfs*2), while the other family showed a previously reported nonsense mutation NM_018136.4: c.9730C>T (rs199422195 (p.Arg3244*)) in ASPM gene. The novel frame-shift mutation (p.Asp3338Valfs*2) in ASPM presumably truncates the protein synthesis that results in loss of armadillo-type fold domain.

    • Author Affiliations

       

      MUZAMMIL AHMAD KHAN1 2 CHRISTIAN WINDPASSINGER3 MUHAMMAD ZEESHAN ALI2 MUHAMMAD ZUBAIR2 4 HADIA GUL5 SAFDAR ABBAS2 SAADULLAH KHAN1 6 MUHAMMAD BADAR2 RAMZI M. MOHAMMAD1 ZAFAR NAWAZ1 7

      1. Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar
      2. Gomal Centre of Biochemistry and Biotechnology,Gomal University Dera Ismail Khan, Khyber-Pakhtoonkhwa 29050, Pakistan
      3. Institute of Human Genetics, Medical University of Graz, Graz 8010, Austria
      4. Department of Cell and Developmental Biology, School of Life Sciences, University of Science and Technology China, Hefei 230026, China
      5. Faculty of Sciences, Department of Biological Sciences, Gomal University Dera Ismail Khan, Khyber-Pakhtoonkhwa 29050, Pakistan
      6. Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat 26000, Khyber Pakhtunkhwa, Pakistan
      7. Diagnostic Genomic Division, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha 3050, Qatar
    • Dates

       
  • Journal of Genetics | News

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