Clinical variability in DYNC2H1-related skeletal ciliopathies includes Ellis-van Creveld syndrome.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
19
08
2022
accepted:
15
12
2022
revised:
17
11
2022
pmc-release:
01
04
2024
medline:
28
4
2023
pubmed:
5
1
2023
entrez:
4
1
2023
Statut:
ppublish
Résumé
Deleterious variants of DYNC2H1 gene are associated with a wide spectrum of skeletal ciliopathies (SC). We used targeted parallel sequencing to analyze 25 molecularly unsolved families with different SCs. Deleterious DYNC2H1 variants were found in six sporadic patients and two monozygotic (MZ) twins. Clinical diagnoses included short rib-polydactyly type 3 in two cases, and asphyxiating thoracic dystrophy (ATD) in one case. Remarkably, clinical diagnosis fitted with EvC, mixed ATD/EvC and short rib-polydactyly/EvC phenotypes in three sporadic patients and the MZ twins. EvC/EvC-like features always occurred in compound heterozygotes sharing a previously unreported splice site change (c.6140-5A>G) or compound heterozygotes for two missense variants. These results expand the DYNC2H1 mutational repertoire and its clinical spectrum, suggesting that EvC may be occasionally caused by DYNC2H1 variants presumably acting as hypomorphic alleles.
Identifiants
pubmed: 36599940
doi: 10.1038/s41431-022-01276-7
pii: 10.1038/s41431-022-01276-7
pmc: PMC10133340
doi:
Substances chimiques
Cytoplasmic Dyneins
EC 3.6.4.2
DYNC2H1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
479-484Informations de copyright
© 2023. The Author(s), under exclusive licence to European Society of Human Genetics.
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