title: Genetic heterogeneity in Pakistani microcephaly families.
abstract: Autosomal recessive primary microcephaly (MCPH) is caused by mutations in at least eight different genes involved either in cell division or DNA repair. Most mutations are identified in consanguine families from Pakistan, Iran and India. To further assess their genetic heterogeneity and mutational spectra, we have analyzed 57 consanguine Pakistani MCPH families. In 34 MCPH families, we detected linkage to five out of the eight well-characterized disease loci and identified mutations in 27 families, leaving seven families without mutations in the coding exons of the presumably underlying MCPH genes. In the MCPH cohort 23 families could not be linked to any of the known loci, pointing to remarkable locus heterogeneity. The majority of mutations were found in ASPM followed by WDR62, CENPJ, CEP152 and MCPH1. One ASPM mutation (p.Trp1326*) was found in as many as eight families suggesting a Pakistani founder mutation. One third of the families were linked to ASPM followed by WDR62 confirming previous data. We identified three novel ASPM mutations, four novel WDR62 mutations, one novel MCPH1 mutation and two novel CEP152 mutations. CEP152 mutations have not been described before in the Pakistani population.
authors: Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology & Genetic Engineering (NIBGE), Faisalabad, Pakistan.
authors: M
authors: M
authors: Sajid Hussain
authors: S
authors: S
authors: Marriam Bakhtiar
authors: M
authors: M
authors: Farooq
authors: I
authors: I
authors: Anjum
authors: E
authors: E
authors: Janzen
authors: M
authors: M
authors: Reza Toliat
authors: H
authors: H
authors: Eiberg
authors: K W
authors: KW
authors: Kjaer
authors: N
authors: N
authors: Tommerup
authors: A A
authors: AA
authors: Noegel
authors: P
authors: P
authors: Nürnberg
authors: S M
authors: SM
authors: Baig
authors: L
authors: L
authors: Hansen
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics; D003241:Consanguinity; D003598:Cytoskeletal Proteins; D005190:Family; D023061:Gene Order; D005808:Genes, Recessive; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D056426:Genetic Loci; D006801:Humans; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D010154:Pakistan
chemical_list: C551028:CEP152 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins; C552527:WDR62 protein, human