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Ectodermal dysplasia (ED) represents a heterogeneous group of genetic disorders characterized by the absence or deformity in two or more of the ectodermal appendages. We have studied an autosomal recessive form of ED in 13 individuals over six generations from an inbred Pakistani family. The clinical features of the affected individuals include highly dystrophic nails and thin hair on scalp, fine eyebrows and eyelashes, and thin body hair. Genome-wide linkage analysis of 390 microsatellite markers mapped the ED gene to the 3.92 cM interval flanked by markers D10S1710 and D10S1741 on chromosome 10q24.32-q25.1. Multipoint linkage analysis generated a maximum logarithm of odds ratio score of 4.79 in the interval D10S1239-D10S1264, which corresponds to 6.35 Mb.

Grebe-type chondrodysplasia exhibits a severe form of limb shortening and appendicular bone dysmorphogenesis. Here we report a family with seven males and six females who inherited the disorder in an autosomal recessive fashion. While the carrier parents did not exhibit any apparent skeletal abnormalities, all affected patients had a similar phenotype with unaffected axial and craniofacial bones. Since mutations in the cartilage-derived morphogenetic protein 1 (CDMP1) gene have been reported in similar acromesomelic chondrodysplasias, we examined genomic DNA from affected and normal subjects for possible mutations in CDMP1. In affected subjects, an insertion of a C at nucleotide 297 of the coding sequence was discovered. This insertion produced a shift in the reading frame at amino acid residue 99, causing premature termination of the polypeptide six amino acids downstream. DNA samples from 41 control subjects did not show this mutation. The truncated CDMP1 protein in these subjects is predicted to cause a total loss of its signaling function. The present report confirms that CDMP1 plays an important role in the regulation of axial bone growth during development and suggests that its absence does not impair other developmental processes., (Copyright 2002 Wiley-Liss, Inc.)