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

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

DESIGN: Case report.

SETTING: Molecular and cytogenetics unit in a university-affiliated hospital.

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

INTERVENTION(S): Molecular cytogenetic analyses and genetic counseling.

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

RESULT(S): 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.

CONCLUSION(S): 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.