Sanjad-sakati and autosomal recessive Kenny-Caffey syndromes are allelic: Evidence for an ancestral founder mutation and locus refinement

The Sanjad-Sakati syndrome (SSS; MIM241410), an autosomal recessive trait c haracterized by congenital hypoparathyroidism, growth and mental retardatio n, seizures, and a characteristic physiognomy, was recently linked to chrom osome area 1q42-q43. SSS resembles the autosomal recessive form of Kenny-Ca ffey syndrome (KCS; MIM244460), with similar manifestations but lacking ost eosclerosis. Since KCS was recently linked to the region 1q42-q43, the poss ibility that this disorder is allelic with SSS was considered. Eight Sanjad -Sakati families from Saudi Arabia were genotyped with polymorphic short ta ndem repeat markers from the SSS/KCS critical region, A maximum multipoint LOD score of 14.32 was obtained at marker D1S2649, confirming linkage of SS S to the same region as autosomal recessive KCS. Haplotype analysis refined the critical region to 2.6 cM and identified a rare haplotype present in a ll the SSS disease alleles, indicative of a common founder. In addition to the assignment of the Saudi SSS and Kuwaiti KCS syndromes to overlapping ge netic intervals, comparison of the haplotypes unexpectedly demonstrated tha t the diseases shared an identical haplotype. This finding, combined with t he clinical similarity between the two syndromes, suggests that the two con ditions are not only allelic but are also caused by the same ancestral muta tion. Am. J. Med. Genet, 85:48-52, 1999, (C) 1009 Wiley-Liss, Inc.