Genetic studies of autosomal recessive primary microcephaly in 33 Pakistani families: Novel sequence variants in ASPM gene

Asma Gul, Muhammad Jawad Hassan, Saqib Mahmood, Wenje Chen, Safa Rahmani, Muhammad Imran Naseer, Lisa Dellefave, Noor Muhammad, Muhammad Arshad Rafiq, Muhammad Ansar, Muhammad Salman Chishti, Ghazanfar Ali, Teepu Siddique, Wasim Ahmad*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Human autosomal recessive primary microcephaly (MCPH) is a rare genetic disorder in which affected individuals are born with reduced brain size. MCPH is genetically heterogeneous, with six loci and four genes reported to date. Mutations in the ASPM gene at the MCPH5 locus appear to be the most common cause of MCPH. For this study, 33 Pakistani families with primary microcephaly were enrolled. Genotyping using microsatellite markers linked to the six known MCPH loci showed the linkage of 18 families to the MCPH5 locus, two to the MCPH2 locus, two to the MCPH4 locus, and one to the MCPH6 locus. The remaining ten families were not linked to any of the known loci. Families linked to the MCPH5 locus were further subjected to screening of the ASPM gene with direct DNA sequencing. Two previously reported variants, 3978G>A (W1326X) and 9557C>G (S3186X), were observed in five Pakistani families. Four novel nonsynonymous sequence variants, 9118insCATT, 9238A>T (L3080X), 9539A>C (Q3180P), and 1260delT-CAAGTC, were found to segregate within four families, but were not observed in 200 Pakistani control chromosomes. One of the variants, 9539A>C (Q3180P), occurred in the IQ 79 domain, but its functional significance awaits definition.

Original languageEnglish (US)
Pages (from-to)105-110
Number of pages6
JournalNeurogenetics
Volume7
Issue number2
DOIs
StatePublished - May 2006

Keywords

  • ASPM mutations
  • MCPH
  • Pakistani families

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Cellular and Molecular Neuroscience

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