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Homozygous Nonsense Mutation in the ASPM Gene Causes MCPH in Consanguineous Pakistani Families

Homozygous Nonsense Mutation in the ASPM Gene Causes MCPH in Consanguineous Pakistani Families

Ansar Ahmed Abbasi1,*, Kathrin Blasius2-4, Imtiaz Ahmed6, Hao Hu7, Sylvie Picker-Minh2-4,8, Muhammad Nasim Khan5, Khalid Hameed1, Aneela Gulnaz1, Zahid Latif5, Abdul Rauf5 and Angela M. Kaindl2-4,8

1Department of Zoology, Mirpur University of Science and Technology, Mirpur 10250, Pakistan
2Institute of Neuroanatomy and Cell Biology, Charité-Universitätsmedizin Berlin, Berlin, Germany
3Berlin Institute of Health, Anna-Louisa-Karsch Strasse 2, 10178, Berlin, Germany
4Center for Chronically Sick Children (Sozialpädiatrisches Zentrum, SPZ), Charité-Universitätsmedizin Berlin, Berlin, Germany
5Department of Zoology, University of Azad Jammu and Kashmir, P.O. Box 13100, Muzaffarabad, Pakistan
6Department of Veterinary and Animal Sciences, University of Poonch Rawalakot, AJK, Pakistan
7Guangzhou Women and Children’s Medical Center, Guangzhou, China
8Department of Pediatric Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany

Ansar Ahmed Abbasi and Kathrin Blasius contributed equally in this study.

*     Corresponding author: ansar.zoology@must.edu.pk

 

Fig. 1.

A, Pedigree of the consanguineous family A of Pakistani descent with two patients affected by microcephaly (□, male; ○, female; ═, consanguineous marriage); B, Sanger sequencing results of patient IV.2 from family A showing a homozygous mutation c.4802C>G in the ASPM gene that leads to a nonsense mutation p.S1601* (red arrow). The parental control III.2 is heterozygous for the ASPM mutation.

Fig. 2.

 A, Pedigree of the consanguineous family B of Pakistani descent with two patients affected by microcephaly, speech delay and motor delay (□, male; ○, female; ═, consanguineous marriage); B, Sanger sequencing results of patient IV.2 from family B showing a homozygous mutation c.4802C>G in the ASPM gene that leads to a nonsense mutation p.S1601* (red arrow). The parental control III.3 is heterozygous for the ASPM mutation.

Fig. 3.

A, the ASPM gene codes for a 3477 aa protein with four protein domains: microtubule binding domain (light grey), CH domain (grey), calmodulin-binding IQ domains (dark grey) and the Armadillo-like domain (brown); B, the nonsense mutation p.S1601* in patients of family A and B lead to a truncated protein, which is missing the Armadillo-like domain and part of the calmodulin-binding IQ domain.

Pakistan Journal of Zoology

December

Vol. 50, Iss. 6, Pages 1999-2398

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