Compound heterozygous ASPM mutations in Pakistani MCPH families
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Compound heterozygous ASPM mutations in Pakistani MCPH families. / Muhammad, Farooq; Mahmood Baig, Shahid; Hansen, Lars; Sajid Hussain, Muhammad; Anjum Inayat, Iram; Aslam, Muhammad; Anver Qureshi, Javed; Toilat, Muhammad; Kirst, Elisabeth; Wajid, Muhammad; Nürnberg, Peter; Eiberg, Hans; Tommerup, Niels; Kjaer, Klaus W.
I: American Journal of Medical Genetics. Part A, Bind 149A, Nr. 5, 2009, s. 926-30.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Compound heterozygous ASPM mutations in Pakistani MCPH families
AU - Muhammad, Farooq
AU - Mahmood Baig, Shahid
AU - Hansen, Lars
AU - Sajid Hussain, Muhammad
AU - Anjum Inayat, Iram
AU - Aslam, Muhammad
AU - Anver Qureshi, Javed
AU - Toilat, Muhammad
AU - Kirst, Elisabeth
AU - Wajid, Muhammad
AU - Nürnberg, Peter
AU - Eiberg, Hans
AU - Tommerup, Niels
AU - Kjaer, Klaus W
N1 - Keywords: Haplotypes; Heterozygote; Humans; Microcephaly; Mutation; Nerve Tissue Proteins; Pedigree
PY - 2009
Y1 - 2009
N2 - Autosomal recessive primary microcephaly (MCPH) is characterized by reduced head circumference (50% of all reported families. In spite of the high frequency of MCPH in Pakistan only one case of compound heterozygosity for mutations in ASPM has been reported yet. In this large MCPH study we ascertained 37 families including 319 persons (140 patients). Haplotype analysis of eight STS markers suggested linkage by homozygosity in 20 families, and re-analysis of single sib ships in the remaining families demonstrated possible compound heterozygosity in two families. Direct sequencing indeed confirmed compound heterozygosity in two and homozygous mutations in 20 families, respectively, showing that up to 10% of families with MCPH caused by ASPM are compound heterozygous. In total we identified 16 different nonsense or frameshift mutations of which 12 were novel thereby increasing the number of mutations in ASPM significantly from 35 to 47. We found no correlation between the severity of the condition and the site of truncation. We suggest that the high frequency of compound heterozygosity observed in this study is taken into consideration as part of future genetic testing and counseling in Pakistani MCPH families.
AB - Autosomal recessive primary microcephaly (MCPH) is characterized by reduced head circumference (50% of all reported families. In spite of the high frequency of MCPH in Pakistan only one case of compound heterozygosity for mutations in ASPM has been reported yet. In this large MCPH study we ascertained 37 families including 319 persons (140 patients). Haplotype analysis of eight STS markers suggested linkage by homozygosity in 20 families, and re-analysis of single sib ships in the remaining families demonstrated possible compound heterozygosity in two families. Direct sequencing indeed confirmed compound heterozygosity in two and homozygous mutations in 20 families, respectively, showing that up to 10% of families with MCPH caused by ASPM are compound heterozygous. In total we identified 16 different nonsense or frameshift mutations of which 12 were novel thereby increasing the number of mutations in ASPM significantly from 35 to 47. We found no correlation between the severity of the condition and the site of truncation. We suggest that the high frequency of compound heterozygosity observed in this study is taken into consideration as part of future genetic testing and counseling in Pakistani MCPH families.
U2 - 10.1002/ajmg.a.32749
DO - 10.1002/ajmg.a.32749
M3 - Journal article
C2 - 19353628
VL - 149A
SP - 926
EP - 930
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 5
ER -
ID: 20875993