The co-occurrence of two rare recessive genetic conditions in apparently unre lated individuals or families is extremely rare. Two geographically distant and apparently unrelated families were identified in which indi...The co-occurrence of two rare recessive genetic conditions in apparently unre lated individuals or families is extremely rare. Two geographically distant and apparently unrelated families were identified in which individuals were simultan eously affected by two rare recessive mendelian syndromes, Papillon-Lefevre syn drome 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 famil ies 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 chro mosome bands 11q14.2-14.3, and studies with linked genetic markers suggested th at 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.展开更多
文摘The co-occurrence of two rare recessive genetic conditions in apparently unre lated individuals or families is extremely rare. Two geographically distant and apparently unrelated families were identified in which individuals were simultan eously affected by two rare recessive mendelian syndromes, Papillon-Lefevre syn drome 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 famil ies 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 chro mosome bands 11q14.2-14.3, and studies with linked genetic markers suggested th at 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.
