title: Discordant phenotypes in a mother and daughter with mosaic supernumerary ring chromosome 19 explained by a de novo 7q36.2 deletion and 7p22.1 duplication.
abstract: We report on a patient with severe intellectual disability, microcephaly, short stature, and dysmorphic features who, based on standard karyotyping, has two cytogenetic abnormalities: an apparently balanced paracentric inversion of chromosome 7, inv(7)(q31.2q36), and a small supernumerary ring chromosome derived entirely of material from chromosome 19. While the inversion was detected in all cells, mosaicism was observed for the ring chromosome. Interestingly, apparently identical cytogenetic abnormalities were detected in the patient's mother, who presented with normal stature, few dysmorphic features, and normal cognition without microcephaly. While the level of mosaicism could not adequately explain the phenotypic discordance, comparative genome hybridization revealed a de novo terminal deletion of chromosome 7, del(7)(q36.2), and a terminal duplication of chromosome 7, dup(7)(p22.1) in the patient. Additional cytogenetic investigation revealed that the patient inherited a recombinant chromosome derived from a cryptic maternal pericentric inversion: inv(7)(p22q36). The patient's distinctive features are consistent with the wide phenotypic spectrum reported in 7p duplication and 7q terminal deletion syndromes. These chromosomal regions contain several candidate genes of clinical significance, including SHH, EN2, and FAM20C. Our findings strongly suggest that our patient's phenotype is largely attributable to partial 7pter trisomy and partial 7qter monosomy rather than mosaic supernumerary ring chromosome 19.
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada. bargiropoulos@cheo.on.ca
authors.forename: Bob
authors.initials: B
authors.lastname: Argiropoulos
authors.forename: Melissa
authors.initials: M
authors.lastname: Carter
authors.forename: Kathy
authors.initials: K
authors.lastname: Brierley
authors.forename: Heather
authors.initials: H
authors.lastname: Hare
authors.forename: Amélie
authors.initials: A
authors.lastname: Bouchard
authors.forename: Walla
authors.initials: W
authors.lastname: Al-Hertani
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Ryan
authors.forename: Judith
authors.initials: J
authors.lastname: Reid
authors.forename: Mark
authors.initials: M
authors.lastname: Basik
authors.forename: Jean
authors.initials: J
authors.lastname: McGowan-Jordan
authors.forename: Gail E
authors.initials: GE
authors.lastname: Graham
mesh_terms: D000328:Adult; D002871:Chromosome Banding; D002872:Chromosome Deletion; D058674:Chromosome Duplication / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D008875:Middle Aged; D009030:Mosaicism; D010641:Phenotype; D012303:Ring Chromosomes