title: Unusual Duplication in the Pericentromeric Region of Chromosome 9 in a Patient with Phenotypic Alterations.
abstract: Several alterations involving the pericentromeric region of chromosome 9 are considered as normal population variants. These heterochromatic variants or heteromorphisms can include 9qh+, 9cen+, 9ph+, 9ph-, inv(9)(p11q13), and other patterns which can only be defined by FISH studies. However, some heteromorphisms have been found more frequently in patients with several clinical disorders. Here, we report on a patient with intellectual disability, language and neurodevelopmental delay, as well as facial dysmorphism and an unusual chromosome 9. While the banding karyotype was indicative of a simple pericentric inversion of one chromosome 9 [46,XX,inv(9)(p12q13)], array comparative genomic hybridization showed a 6-Mb duplication, including 22 genes: arr[hg19] 9p13.1p11.2(38,869,901- 44,870,714)×3 dn. Molecular cytogenetics using a panel of probes specific for the pericentromeric region of chromosome 9 showed an unusual, rearranged chromosome 9, der(9)(pter→p11.2::q21.11→q12::p11.2→p13.2::q12→p11.2::q21.11→qter), that has not been described before. The patient's phenotypic alterations are probably due to the de novo 6-Mb 9p duplication, although a review of similar cases showed some reports considering this duplication in the euchromatic region as a benign variant. Interestingly, this is the first report of a possible adverse inversion loop formation due to a known heteromorphic pericentric inversion present in the phenotypically normal father of the patient.
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Andréa C M
authors.initials: AC
authors.lastname: Malinverni
authors.forename: Mileny E
authors.initials: ME
authors.lastname: Colovati
authors.forename: Ana B A
authors.initials: AB
authors.lastname: Perez
authors.forename: Thamy P
authors.initials: TP
authors.lastname: Caneloi
authors.forename: Hélio R
authors.initials: HR
authors.lastname: Oliveira
authors.forename: Nadezda
authors.initials: N
authors.lastname: Kosyakova
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.forename: Ahmed B
authors.initials: AB
authors.lastname: Hamid
authors.forename: Maria I
authors.initials: MI
authors.lastname: Melaragno
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000293:Adolescent; D002503:Centromere / Q000235:genetics; D002871:Chromosome Banding; D058674:Chromosome Duplication; D007446:Chromosome Inversion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D008297:Male; D010641:Phenotype