Possible incomplete penetrance of Xq28 int22h-1/int22h-2 duplication.

CLIC2 RAB39B Xq28 duplication Xq28 int22h‐1/int22h‐2 duplication X‐linked intellectual disability incomplete penetrance

Journal

Clinical genetics

ISSN: 1399-0004

Titre abrégé: Clin Genet

Pays: Denmark

ID NLM: 0253664

Informations de publication

Date de publication:
01 Apr 2024

Historique:

revised: 16 03 2024

received: 03 12 2023

accepted: 18 03 2024

medline: 2 4 2024

pubmed: 2 4 2024

entrez: 1 4 2024

Statut: aheadofprint

Résumé

Xq28 int22h-1/int22h-2 duplication is the result of non-allelic homologous recombination between int22h-1/int22h-2 repeats separated by 0.5 Mb. It is responsible for a syndromic form of intellectual disability (ID), with recurrent infections and atopic diseases. Minor defects, nonspecific facial dysmorphic features, and overweight have also been described. Half of female carriers have been reported with ID, whereas all reported evaluated born males present mild to moderate ID, suggesting complete penetrance. We collected data on 15 families from eight university hospitals. Among them, 40 patients, 21 females (one fetus), and 19 males (two fetuses), were carriers of typical or atypical Xq28 int22h-1/int22h-2 duplication. Twenty-one individuals were considered asymptomatic (16 females and 5 males), without significantly higher rate of recurrent infections, atopia, overweight, or facial dysmorphism. Approximately 67% live-born males and 23% live-born female carriers of the typical duplication did not have obvious signs of intellectual disability, suggesting previously undescribed incomplete penetrance or low expression in certain carriers. The possibility of a second-hit or modifying factors to this possible susceptibility locus is yet to be studied but a possible observational bias should be considered in assessing such challenging X-chromosome copy number gains. Additional segregation studies should help to quantify this newly described incomplete penetrance.

Identifiants

DOI: 10.1111/cge.14525 PMID: 38561231

pubmed: 38561231

doi: 10.1111/cge.14525

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Informations de copyright

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