title: Previously described sequence variant in CDK5RAP2 gene in a Pakistani family with autosomal recessive primary microcephaly.
abstract: BACKGROUND
  Autosomal Recessive Primary Microcephaly (MCPH) is a disorder of neurogenic mitosis. MCPH leads to reduced cerebral cortical volume and hence, reduced head circumference associated with mental retardation of variable degree. Genetic heterogeneity is well documented in patients with MCPH with six loci known, while pathogenic sequence variants in four respective genes have been identified so far. Mutations in CDK5RAP2 gene at MCPH3 locus have been least involved in causing MCPH phenotype.
  
  
  METHODS
  All coding exons and exon/intron splice junctions of CDK5RAP2 gene were sequenced in affected and normal individuals of Pakistani MCPH family of Kashmiri origin, which showed linkage to MCPH3 locus on chromosome 9q33.2.
  
  
  RESULTS
  A previously described nonsense mutation [243 T>A (S81X)] in exon 4 of CDK5RAP2 gene has been identified in the Pakistani family, presented here, with MCPH Phenotype. Genomic and cDNA sequence comparison revealed that the exact nomenclature for this mutation is 246 T>A (Y82X).
  
  
  CONCLUSIONS
  Recurrent observation of Y82X mutation in CDK5RAP2 gene in this Pakistani family may be a sign of confinement of a rare ancestral haplotype carrying this pathogenic variant within Northern Pakistani population, as this has not been reported in any other population.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. mjhassan@bs.qau.edu.pk
authors.forename: Muhammad Jawad
authors.initials: MJ
authors.lastname: Hassan
authors.forename: Maryam
authors.initials: M
authors.lastname: Khurshid
authors.forename: Zahid
authors.initials: Z
authors.lastname: Azeem
authors.forename: Peter
authors.initials: P
authors.lastname: John
authors.forename: Ghazanfar
authors.initials: G
authors.lastname: Ali
authors.forename: Muhammad Salman
authors.initials: MS
authors.lastname: Chishti
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000293:Adolescent; D000328:Adult; D018797:Cell Cycle Proteins; D002899:Chromosomes, Human, Pair 9; D018389:Codon, Nonsense; D005260:Female; D005808:Genes, Recessive; D014644:Genetic Variation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: C405929:CDK5RAP2 protein, human; D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins