Molecular diagnosis and novel genes and phenotypes in a pediatric thoracic insufficiency cohort.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
18 01 2023
18 01 2023
Historique:
received:
26
05
2022
accepted:
05
01
2023
entrez:
18
1
2023
pubmed:
19
1
2023
medline:
21
1
2023
Statut:
epublish
Résumé
Thoracic insufficiency syndromes are a genetically and phenotypically heterogeneous group of disorders characterized by congenital abnormalities or progressive deformation of the chest wall and/or vertebrae that result in restrictive lung disease and compromised respiratory capacity. We performed whole exome sequencing on a cohort of 42 children with thoracic insufficiency to elucidate the underlying molecular etiologies of syndromic and non-syndromic thoracic insufficiency and predict extra-skeletal manifestations and disease progression. Molecular diagnosis was established in 24/42 probands (57%), with 18/24 (75%) probands having definitive diagnoses as defined by laboratory and clinical criteria and 6/24 (25%) probands having strong candidate genes. Gene identified in cohort patients most commonly encoded components of the primary cilium, connective tissue, and extracellular matrix. A novel association between KIF7 and USP9X variants and thoracic insufficiency was identified. We report and expand the genetic and phenotypic spectrum of a cohort of children with thoracic insufficiency, reinforce the prevalence of extra-skeletal manifestations in thoracic insufficiency syndromes, and expand the phenotype of KIF7 and USP9X-related disease to include thoracic insufficiency.
Identifiants
pubmed: 36653407
doi: 10.1038/s41598-023-27641-0
pii: 10.1038/s41598-023-27641-0
pmc: PMC9849333
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
991Subventions
Organisme : NIDDK NIH HHS
ID : K08 DK128606
Pays : United States
Informations de copyright
© 2023. The Author(s).
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