title: 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).
abstract: Familial reciprocal translocations are generally without phenotypic effect, although there is some evidence for a small excess of mental retardation and congenital malformations (MR/CM) in children carrying familial reciprocal translocations. Possible mechanisms whereby such translocations could have a phenotypic effect include cryptic unbalanced rearrangements, uniparental disomy, and disruption of putative genes at the breakpoints, unmasking recessive alleles on the normal homologs. Mosaicism for a supernumerary derivative chromosome in a carrier of a familial reciprocal translocation has not yet 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 mother. Cytogenetic analysis of peripheral blood lymphocytes showed a balanced karyotype in all 32 analyzed metaphase spreads. Molecular genetic analysis was consistent with biparental origin of the normal homologs. In metaphase spreads 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). Several possible segregation modes at meiosis I followed by meiosis II or postzygotic nondisjunction of the der(22) might have led to this unusual chromosomal mosaicism. We propose hidden mosaicism as a possible cause for MR/CM in patients who apparently carry a balanced familial reciprocal translocation.
authors.affiliation: Division of Medical Genetics, University of Tübingen, Tübingen, Germany. andreas.dufka@uni-tuebingen.de
authors.forename: A
authors.initials: A
authors.lastname: Dufke
authors.forename: H
authors.initials: H
authors.lastname: Mayrhofer
authors.forename: H
authors.initials: H
authors.lastname: Enders
authors.forename: P
authors.initials: P
authors.lastname: Kaiser
authors.forename: M
authors.initials: M
authors.lastname: Leipoldt
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000503:physiopathology; D000293:Adolescent; D002675:Child, Preschool; D002871:Chromosome Banding; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003434:Crossing Over, Genetic / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D007621:Karyotyping; D008297:Male; D009030:Mosaicism / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*