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Coinheritance of two rare genodermatoses (Papillon–Lefèvre syndrome and oculocutaneous albinism type 1) in two families: a genetic study
Author(s) -
Hewitt C.,
Wu CL.,
Hattab F.N.,
Amin W.,
Ghaffar K.A.,
Toomes C.,
Sloan P.,
Read A.P.,
James J.A.,
Thakker N.S.
Publication year - 2004
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2004.06237.x
Subject(s) - christian ministry , oculocutaneous albinism , library science , medicine , family medicine , sociology , genetics , albinism , biology , political science , law , computer science
Summary 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–Lefèvre 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.