title: A novel deletion mutation in the DSG4 gene underlies autosomal recessive hypotrichosis with variable phenotype in two unrelated consanguineous families.
abstract: BACKGROUND
  Autosomal recessive hypotrichosis is a rare human hereditary disorder presenting as sparse scalp hair or as woolly hair occurring on various parts of the body. Various forms of isolated hypotrichosis have been reported to date. Mutations in at least 11 genes have been reported to cause hypotrichosis.
  
  
  OBJECTIVE
  To investigate the clinical and genetic basis of autosomal recessive hypotrichosis in two unrelated consanguineous families.
  
  
  METHODS
  Genotyping by highly polymorphic microsatellite markers established linkage in both families to the DSG4 gene on chromosome 18q21. PCR amplification of exons and intron-exon borders of the DSG4 gene was performed, and the products sequenced to search for disease-causing sequence variants.
  
  
  RESULTS
  Clinical investigation revealed typical hypotrichosis in the affected members of one family, while other affected members showed presence of monilethrix-like scalp hair. Sequence analysis of DSG4 revealed a novel deletion mutation (c.85-1_191del) in the affected subjects of both families.
  
  
  CONCLUSIONS
  This study further extends the body of evidence that mutations in the DSG4 gene result in both hypotrichosis and monilethrix-like scalp hair.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: A
authors.initials: A
authors.lastname: Ullah
authors.forename: S I
authors.initials: SI
authors.lastname: Raza
authors.forename: R H
authors.initials: RH
authors.lastname: Ali
authors.forename: A K
authors.initials: AK
authors.lastname: Naveed
authors.forename: A
authors.initials: A
authors.lastname: Jan
authors.forename: S D A
authors.initials: SD
authors.lastname: Rizvi
authors.forename: R
authors.initials: R
authors.lastname: Satti
authors.forename: W
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000505:Alopecia / Q000151:congenital* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D051182:Desmogleins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D017384:Sequence Deletion
chemical_list: C473409:DSG4 protein, human; D051182:Desmogleins