Universität zu Köln

Ahmad, I., Baig, S. M., Abdulkareem, A. R., Hussain, M. S., Sur, I., Toliat, M. R., Nuernberg, G., Dalibor, N., Moawia, A., Waseem, S. S., Asif, M., Nagra, H., Sher, M., Khan, M. M. A., Hassan, I., Rehman, S. Ur, Thiele, H., Altmueller, J., Noegel, A. A. and Nuernberg, P. (2017). Genetic heterogeneity in Pakistani microcephaly families revisited. Clin. Genet., 92 (1). S. 62 - 69. HOBOKEN: WILEY. ISSN 1399-0004

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Abstract

Autosomal recessive primary microcephaly (MCPH) is a rare and heterogeneous genetic disorder characterized by reduced head circumference, low cognitive prowess and, in general, architecturally normal brains. As many as 14 different loci have already been mapped. We recruited 35 MCPH families in Pakistan and could identify the genetic cause of the disease in 31 of them. Using homozygosity mapping complemented with whole-exome, gene panel or Sanger sequencing, we identified 12 novel mutations in 3 known MCPH-associated genes-9 in ASPM, 2 in MCPH1 and 1 in CDK5RAP2. The 2 MCPH1 mutations were homozygous microdeletions of 164,250 and 577,594bp, respectively, for which we were able to map the exact breakpoints. We also identified four known mutations three in ASPM and one in WDR62. The latter was initially deemed to be a missense mutation but we demonstrate here that it affects splicing. As to ASPM, as many as 17 out of 27 MCPH5 families that we ascertained in our sample were found to carry the previously reported founder mutation p.Trp1326*. This study adds to the mutational spectra of four known MCPH-associated genes and updates our knowledge about the genetic heterogeneity of MCPH in the Pakistani population considering its ethnic diversity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ahmad, I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baig, S. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Abdulkareem, A. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hussain, M. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sur, I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Toliat, M. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dalibor, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moawia, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Waseem, S. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Asif, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nagra, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sher, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Khan, M. M. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hassan, I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rehman, S. Ur UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Noegel, A. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-226513
DOI:	10.1111/cge.12955
Journal or Publication Title:	Clin. Genet.
Volume:	92
Number:	1
Page Range:	S. 62 - 69
Date:	2017
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1399-0004
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MENTAL-RETARDATION; MCPH1 DELETION; ASPM GENE; MUTATIONS; CYTOKINESIS; KINASE; BRAIN; CIT Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22651