title: Coinheritance of two rare genodermatoses (Papillon-Lefèvre syndrome and oculocutaneous albinism type 1) in two families: a genetic study.
abstract: The co-occurrence of two rare recessive genetic conditions in apparently unrelated individuals or families is extremely rare. Two geographically distant and apparently unrelated families were identified in which individuals were simultaneously affected by two rare recessive mendelian syndromes, Papillon-Lefevre syndrome and type 1 oculocutaneous albinism. The families were tested for mutations in the causative genes, cathepsin C (CTSC) and tyrosinase (TYR), respectively, by direct sequencing. To assess the relationship of the two families, both families were tested for polymorphisms at eight microsatellite markers spanning both CTSC and TYR loci. Independent mutations (c.318-1G-->A and c.817G-->C/p.W272C) were identified in CTSC and TYR, respectively, that were shared by the affected individuals in both families. The two affected genes lie close together on chromosome bands 11q14.2-14.3, and studies with linked genetic markers suggested that the families shared a small chromosomal segment carrying both mutations that had been transmitted intact from a remote common ancestor. The co-occurrence of the two rare diseases in multiple families depends on their shared chromosomal location, but not on any shared pathogenic mechanism.
authors.affiliation: Unit of Medical Genetics, University of Manchester and the Regional Molecular Genetics Service, St Mary's Hospital, Manchester M13 0JH, U.K.
authors.forename: C
authors.initials: C
authors.lastname: Hewitt
authors.forename: C-L
authors.initials: CL
authors.lastname: Wu
authors.forename: F N
authors.initials: FN
authors.lastname: Hattab
authors.forename: W
authors.initials: W
authors.lastname: Amin
authors.forename: K A
authors.initials: KA
authors.lastname: Ghaffar
authors.forename: C
authors.initials: C
authors.lastname: Toomes
authors.forename: P
authors.initials: P
authors.lastname: Sloan
authors.forename: A P
authors.initials: AP
authors.lastname: Read
authors.forename: J A
authors.initials: JA
authors.lastname: James
authors.forename: N S
authors.initials: NS
authors.lastname: Thakker
mesh_terms: D000328:Adult; D016115:Albinism, Oculocutaneous / Q000150:complications / Q000235:genetics*; D001483:Base Sequence; D020789:Cathepsin C / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008297:Male; D014442:Monophenol Monooxygenase / Q000235:genetics; D009154:Mutation; D010214:Papillon-Lefevre Disease / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D035583:Rare Diseases / Q000150:complications / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D014442:Monophenol Monooxygenase; D020789:Cathepsin C