Brachydactyly type B: clinical description, genetic mapping to chromosome 9q, and evidence for a shared ancestral mutation.
Autosomal dominant brachydactyly type B (BDB) is characterized by nail aplasia with rudimentary or absent distal and middle phalanges. We describe two unrelated families with BDB. One family is English; the other family is Canadian but of English ancestry. We assigned the BDB locus in the Canadian family to an 18-cM interval on 9q, using linkage analysis (LOD score 3.5 at recombination fraction [theta] 0, for marker D9S938). Markers across this interval also cosegregated with the BDB phenotype in the English family (LOD score 2.1 at straight theta=0, for marker D9S277). Within this defined interval is a smaller (7.5-cM) region that contains 10 contiguous markers whose disease-associated haplotype is shared by the two families. This latter result suggests a common founder among families of English descent that are affected with BDB.
Gong
Y
Y
Department of Genetics and Center for Human Genetics, Case WesternReserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH, USA.
Chitayat
D
D
Kerr
B
B
Chen
T
T
Babul-Hirji
R
R
Pal
A
A
Reiss
M
M
Warman
M L
ML
D030201:Activin Receptors, Type I; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D005260:Female; D005385:Fingers / Q000002:abnormalities*; D005532:Foot Deformities, Congenital / Q000235:genetics* / Q000503:physiopathology; D005799:Genes, Dominant; D006228:Hand Deformities, Congenital / Q000235:genetics* / Q000503:physiopathology; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D014034:Toes / Q000002:abnormalities*