title: Homozygosity for constitutional chromosomal rearrangements: a systematic review with reference to origin, ascertainment and phenotype.
abstract: Chromosomal translocations and inversions are present in ∼0.6-1% of individuals. Although the majority are inherited, and the familial transmission across generations is well reported, reports of homozygosity are relatively rare, with most data in the form of individual case reports. A systematic review of all published cases was performed with particular attention to origin, ascertainment and phenotype of the reported homozygosity. A total of 10 cases of Robertsonian translocation (RBT), 6 reciprocal translocation and 19 cases of inversion homozygosity were identified. In RBT homozygosity, the majority of individuals are phenotypically normal, arise from inbreeding within a family that carries a familial translocation, and are ascertained following identification of an existing familial rearrangement rather than any feature specific to the homozygosity. In addition, they are fertile and as expected, their offspring are heterozygous for the translocation. For reciprocal translocations, homozygosity arises in individuals born to related parents from a family who harbor a unique familial translocation. Ascertainment is following investigation of phenotypic abnormalities resulting from consanguinity per se and/or the unmasking of a specific gene mutation. For chromosomal inversions, homozygosity may originate from either related or non-consanguinous parentage. Although many cases are ascertained because of an associated phenotypic abnormality, a high proportion of cases are of normal phenotype and a direct causal relationship is uncertain. There are fewer reports of both Robertsonian and inversion homozygosity than may be expected from the relative frequencies of each class within the population.
authors.affiliation: de l'immeuble 3, Centre d'Affaires Poincaré, Nice, France. iain.oneill@hotmail.com
authors.forename: Iain D
authors.initials: ID
authors.lastname: O'Neill
mesh_terms: D003241:Consanguinity; D016206:Databases, Bibliographic; D005192:Family Health; D005260:Female; D015321:Gene Rearrangement; D006720:Homozygote; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D014178:Translocation, Genetic