Clinical variability in DYNC2H1-related skeletal ciliopathies includes Ellis-van Creveld syndrome. in European journal of human genetics : EJHG / Eur J Hum Genet. 2023 Jan 4. doi: 10.1038/s41431-022-01276-7.

2023
ASL Alessandria

Tipo pubblicazione

Journal Article

Autori/Collaboratori (29)Vedi tutti...

Piceci-Sparascio F
Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Brunetti-Pierri N
Pediatric Hospital, Tortona, Italy.
Novelli A
Department of Translational Medicine, Section of Pediatrics, Federico II University, Naples, Italy.

et alii...

Abstract

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.

Accesso banca dati bibliografica

PMID : 36599940

DOI : 10.1038/s41431-022-01276-7