Evidence that Smith-McCort dysplasia and Dyggve-Melchior-Clausen dysplasia are allelic disorders that result from mutations in a gene on chromosome 18q12.
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.
Ehtesham
Nadia
N
Medical Genetics-Birth Defects Center, Ahmanson Department of Pediatrics, Cedars-Sinai Research Institute, Los Angeles, CA 90048, USA.
Cantor
Rita M
RM
King
Lily M
LM
Reinker
Kent
K
Powell
Berkley R
BR
Shanske
Alan
A
Unger
Sheila
S
Rimoin
David L
DL
Cohn
Daniel H
DH
D000483:Alleles; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree