Brachydactyly type B (BDB), an autosomal dominant disorder, is the most sev
ere of the brachydactylies and is characterized by hypoplasia or absence of
the terminal portions of the index to little fingers, usually with absence
of the nails. The thumbs may be of normal length but are often flattened a
nd occasionally are bifid. The feet are similarly but less severely affecte
d. We have per formed a genomewide linkage analysis of three families with
BDB, two English and one Portugese. The two English families show linkage t
o the same region on chromosome 9 (combined multipoint maximum LOD score 8.
69 with marker D9S257). The 16-cM disease interval is defined by recombinat
ions with markers D9S1680 and D9S1786. These two families share an identica
l disease haplotype over 18 markers, inclusive of D9S278-D9S280. This provi
des strong evidence that the English families have the same ancestral mutat
ion, which reduces the disease interval to <12.7 cM between markers D9S257
and D9S1851 in chromosome band 9q22. In the Portuguese family, we excluded
linkage to this region, a result indicating that BDB is genetically heterog
eneous. Reflecting this, there were atypical clinical features in this fami
ly, with shortening of the thumbs and absence or hypoplasia of the nails of
the thumb and hallux. These results enable a refined classification of BDB
and identify a novel locus for digit morphogenesis in 9q22.