The authors declare no conflict of interest.
Genetic heterogeneity in Pakistani microcephaly families
Article first published online: 7 AUG 2012
© 2012 John Wiley & Sons A/S
Volume 83, Issue 5, pages 446–451, May 2013
How to Cite
Genetic heterogeneity in Pakistani microcephaly families, , , , , , , , , , , , .
These authors contributed equally in this work.
- Issue published online: 5 APR 2013
- Article first published online: 7 AUG 2012
- Accepted manuscript online: 6 JUL 2012 01:30PM EST
- Manuscript Revised: 4 JUL 2012
- Manuscript Accepted: 4 JUL 2012
- Manuscript Received: 20 APR 2012
- Higher Education Commission (HEC) of Pakistan
- German Academic Exchange Service (DAAD)
- Danish National Research Foundation
- Lundbeck Foundation
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.