title: Mutation analysis of the ASPM gene in 18 Pakistani families with autosomal recessive primary microcephaly.
abstract: Autosomal recessive primary microcephaly (MCPH) is a rare neurological disorder, in which the patients exhibit reduced occipital frontal head circumference (>3 standard deviations) and mild-to-severe mental retardation. Autosomal recessive primary microcephaly is genetically heterogeneous and 7 loci have been reported to date. Mutations in ASPM (abnormal spindle-like, microcephaly associated) gene are the most common cause of autosomal recessive primary microcephaly in the majority of the reported families. In the current investigation, we have located and studied 21 families with autosomal recessive primary microcephaly. Genotyping using polymorphic microsatellite markers linked to 7 autosomal recessive primary microcephaly loci revealed linkage of 18 families to the MCPH5 locus. Sequence analysis of the ASPM gene in 18 linked families detected 2 novel nonsense mutations (c.2101C>T/p.Q701X; c.9492T>G/p.Y3164X) in 2 families and 2 novel deletion mutations (c.6686delGAAA/p.R2229TfsX9; c.77delG/p.G26AfsX41) in 2 other families. Three previously described mutations (c.3978G>A/p.W1326X; c.1260delTCAAGTC/p.S420SfsX32; c.9159delA/p.K3053NfsX4) were also detected in 11 families. These identified mutations extended the body of evidence implicating the ASPM gene in the pathogenesis of human hereditary primary microcephaly.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Rizwana
authors.initials: R
authors.lastname: Kousar
authors.forename: Hira
authors.initials: H
authors.lastname: Nawaz
authors.forename: Maryam
authors.initials: M
authors.lastname: Khurshid
authors.forename: Ghazanfer
authors.initials: G
authors.lastname: Ali
authors.forename: Saad Ullah
authors.initials: SU
authors.lastname: Khan
authors.forename: Hina
authors.initials: H
authors.lastname: Mir
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ayub
authors.forename: Abdul
authors.initials: A
authors.lastname: Wali
authors.forename: Nadir
authors.initials: N
authors.lastname: Ali
authors.forename: Musharraf
authors.initials: M
authors.lastname: Jelani
authors.forename: Sulman
authors.initials: S
authors.lastname: Basit
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ansar
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010154:Pakistan
chemical_list: C467202:ASPM protein, human; D009419:Nerve Tissue Proteins