Evidence that Smith-McCort dysplasia and Dyggve-Melchior-Clausen dysplasia are allelic disorders that result from mutations in a gene on chromosome 18q12.

Abstract

Smith-McCort dysplasia is a rare autosomal recessive osteochondrodysplasia characterized by short limbs and a short trunk with a barrel-shaped chest. The radiographic phenotype includes platyspondyly, generalized abnormalities of the epiphyses and metaphyses, and a distinctive lacy appearance of the iliac crest. We performed a genomewide scan in a consanguineous family from Guam and found evidence of linkage to loci on chromosome 18q12. Analysis of a second, smaller family was also consistent with linkage to this region, producing a maximum combined two-point LOD score of 3.04 at a recombination fraction of 0 for the marker at locus D18S450. A 10.7-cM region containing the disease gene was defined by recombination events in two affected individuals in the larger family. Furthermore, all affected children in the larger family were homozygous for a subset of marker loci within this region, defining a 1.5-cM interval likely to contain the defective gene. Analysis of three small, unrelated families with Dyggve-Melchior-Clausen syndrome, a radiographically identical disorder with the additional clinical finding of mental retardation, provided evidence of linkage to the same region, a result consistent with the hypothesis that the two disorders are allelic.

• Authors: Nadia Ehtesham, Rita M Cantor, Lily M King, Kent Reinker, Berkley R Powell, Alan Shanske, Sheila Unger, David L Rimoin, Daniel H Cohn
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 71 Issue 4 Pg. 947-51 (Oct 2002) ISSN: 0002-9297 [Print] United States
• PMID: 12161821 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Topics

• Alleles
• Chromosome Mapping
• Chromosomes, Human, Pair 18
• Female
• Humans
• Male
• Mutation
• Osteochondrodysplasias (genetics)
• Pedigree