Ring chromosome 21 and reproductive pattern: a familial case and review of the literature

To characterize a ring chromosome 21 found in an infertile woman and in her mother.

Case report.

Molecular and cytogenetics unit in a university-affiliated hospital.

A 32-year-old infertile woman, presenting a normal female phenotype without clinical signs or major dysmorphisms.

Molecular cytogenetic analyses and genetic counseling.

Structure of chromosome ring 21 (r21) was better defined by fluorescent in situ hybridization and array comparative genomic hybridization.

Proband chromosomal analysis detected a mosaicism with three cell lines: one with a chromosome ring 21 (94%), one 45,XX, -21 (4%), and one with a dicentric ring (2%). This ring was inherited from her mother, whose karyotype was 46,XX, r(21)/45,XX, -21 [98%, 2%]. In both cases, the ring breakpoint was in band 21q22.3, with a deletion of about 3.4 Mb.

When a new case of r(21) is found, an accurate molecular definition of the deletion extent is mandatory and prenatal diagnosis should be suggested in case of pregnancy. Even if a strict genotype-phenotype correlation is not easy, mainly owing to a paucity of molecularly defined cases and to the mosaicism problems, prenatal investigations allow excluding chromosome 21 nondisjunction or rearrangements of r(21) that can have a dramatic effect on the fetus phenotype.