Unusual chromosomal mosaicism as a cause of mental retardation and congenital malformations in a familial reciprocal translocation carrier, t(17;22)(q24.2;q11.23)

Familial reciprocal translocations are generally without phenotypic effect, although there is some evidence for a small excess of mental retardation a nd congenital malformations (MR/CM) in children carrying familial reciproca l translocations. Possible mechanisms whereby such translocations could hav e a phenotypic effect include cryptic unbalanced rearrangements.. uniparent al disomy, and disruption of putative genes at the breakpoints, unmasking r ecessive alleles on the normal homologs. Mosaicism for a supernumerary deri vative chromosome in a carrier of a familial reciprocal translocation has n ot vet been described. We report a boy presenting with MR/CM and a familial reciprocal translocation. t(17;22)(q24.2;q11.23), inherited from the mothe r. Cytogenetic analysis of peripheral blood lymphocytes showed a balanced k aryotype in all 32 analyzed metaphase spreads. Molecular genetic analysis w as consistent with biparental origin of the normal homologs. In metaphase s preads from skin fibroblasts a supernumerary chromosome was found in all 24 cells analyzed and could be identified as der(22)t(17;22)(q24.2;q11.23). S everal possible segregation modes at meiosis I followed by meiosis II or po stzygotic nondisjunction of the der(22) might have led to this unusual chro mosomal mosaicism. We propose hidden mosaicism as a possible cause for MR/C M in patients who apparently carry a balanced familial reciprocal transloca tion. Copyright (C) 2001 S. Karger AG, Basel.