Breakpoint analysis of a familial balanced translocation t(2;8)(q31;p21) associated with mesomelic dysplasia.

Mesomelic dysplasia (MD) is characterised by mildly short stature and shortening of the middle segments of the limbs. There are several subtypes of MD including dyschondrosteosis (Leri-Weill type), Langer type, Nivergelt type, Robinow type, Reinhardt type, Kozlowski-Reardon type, Werner type, and mesomelic dysplasia with synostoses. Ventruto et al reported an Italian family in which four members with a type of MD and vertebral abnormalities had a balanced translocation t(2;8)(q32;p13), which turned out to be t(2;8)(q31;p21) using our improved banding techniques, but three other phenotypically normal members were karyotypically normal. Thus, this type of MD seemed causally related or linked to the translocation. The female proband in the family had a short forearm with bowed and malformed radius, cubitus valgus with limited extension and supination, Madelungtype wrist deformity, atlantoaxial fusion, spina bifida occulta in the lumbosacral region, and the translocation. Kantaputra et al reported a large Thai family with another type of MD, Kantaputra type (MDK), similar to but with more severe manifestations than the MD in the Italian patients. MDK showed mildly short stature, shortening of the forearm/lower leg, carpal/tarsal synostosis, and dorsolateral foot deviation. Our previous linkage analysis of the Thai family using positional information from the translocation breakpoints in the Italian family showed that chromosome 2q24-q32, spanning about a 22.7 cM region, is implicated in MDK. The analysis also suggested that both conditions in the two families are identical or allelic. Furthermore, the HOXD cluster that is related to limb development has been mapped to 2q31. This led us to characterise the 2q31 breakpoint in the Italian family. Here we report the results of the breakpoint analysis.