Inv21p12q22del21q22 and intellectual disability

• Type: Article in International Scientific Journal
• Date: 2013

Authors

oliveira, r (Author) Other; doria, s (Author) FMUP; madureira, c (Author) Other; lima, v (Author) Other; almeida, c (Author) Other; pinho, mj (Author) Other; ramalho, c (Author) FMUP; matoso, e (Author) Other; barros, a (Author) FMUP; carreira, im (Author) Other; moura, cp (Author) FMUP

Journal

Title: Gene

Vol. 517

Pages: 120-124

ISSN: 0378-1119

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 1 Citation

Scopus - 2 Citations

Scientific classification

FOS: Natural sciences > Earth and related Environmental sciences

Other information

Authenticus ID: P-002-00P

DOI: 10.1016/j.gene.2012.12.045

Abstract (EN): Chromosomal rearrangements are common in humans. Pericentric inversions are among the most frequent aberrations (1-2%). Most inversions are balanced and do not cause problems in carriers unless one of the breakpoints disrupts important functional genes, has near submicroscopic copy number variants or hosts "cryptic" complex chromosomal rearrangements. Pericentric inversions can lead to imbalance in offspring. Less than 3% of Down syndrome patients have duplication as a result of parental pericentric inversion of chromosome 21. We report a family with an apparently balanced pericentric inversion of chromosome 21. The proband, a 23-year-old female was referred for prenatal diagnosis at 16 weeks gestation because of increased nuchal translucency. She has a familial history of Down's syndrome and moderate intellectual disability, a personal history of four spontaneous abortions and learning difficulties. Peripheral blood and amniotic fluid samples were collected to perform proband's and fetus' cytogenetic analyses. Additionally, another six family members were evaluated and cytogenetic analysis was performed. Complementary FISH and MLPA studies were carried out. An apparent balanced chromosome 21 pericentric inversion was observed in four family members, two revealed a recombinant chromosome 21 with partial trisomy, and one a full trisomy 21 with an inverted chromosome 21. Array CGH analysis was performed in the mother and the brother's proband. MLPA and aCGH studies identified a deletion of about 1.7 Mb on the long arm of inverted chromosome 21q22.11. We believe the cause of the intellectual disability/learning difficulties observed in the members with the inversion is related to this deletion. The recombinant chromosome 21 has a partial trisomy including the DSCR with no deletion. The risk for carriers of having a child with multiple malformations/intellectual disability is about 30% depending on whether and how this rearrangement interferes with meiosis.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5