TY - JOUR
T1 - Genetic studies of autosomal recessive primary microcephaly in 33 Pakistani families
T2 - Novel sequence variants in ASPM gene
AU - Gul, Asma
AU - Hassan, Muhammad Jawad
AU - Mahmood, Saqib
AU - Chen, Wenje
AU - Rahmani, Safa
AU - Naseer, Muhammad Imran
AU - Dellefave, Lisa
AU - Muhammad, Noor
AU - Rafiq, Muhammad Arshad
AU - Ansar, Muhammad
AU - Chishti, Muhammad Salman
AU - Ali, Ghazanfar
AU - Siddique, Teepu
AU - Ahmad, Wasim
PY - 2006/5/1
Y1 - 2006/5/1
N2 - 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.
AB - 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.
KW - ASPM mutations
KW - MCPH
KW - Pakistani families
UR - http://www.scopus.com/inward/record.url?scp=33646417060&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646417060&partnerID=8YFLogxK
U2 - 10.1007/s10048-006-0042-4
DO - 10.1007/s10048-006-0042-4
M3 - Article
C2 - 16673149
AN - SCOPUS:33646417060
VL - 7
SP - 105
EP - 110
JO - Neurogenetics
JF - Neurogenetics
SN - 1364-6745
IS - 2
ER -