Format

Send to

Choose Destination
Congenit Anom (Kyoto). 2015 Aug;55(3):155-7. doi: 10.1111/cga.12098.

Novel compound heterozygous mutations in DYNC2H1 in a patient with severe short-rib polydactyly syndrome type III phenotype.

Author information

1
Department of Pediatrics, Asahikawa Medical University, Hokkaido, Japan.

Abstract

Short-rib polydactyly syndrome type III is an autosomal recessive lethal skeletal ciliopathy, which is phenotypically similar to nonlethal asphyxiating thoracic dystrophy. Mutations in DYNC2H1 have been identified in both of these disorders, indicating that they are variants of a single disorder. However, short-rib polydactyly syndrome type III is the more severe variant. Here, we report novel compound heterozygous mutations in DYNC2H1 (p.E1894fsX10 and p.R3004C) in a patient with typical short-rib polydactyly syndrome type III phenotype. R3004 is located within the microtubule-binding domain of DYNC2H1, and its substitution is predicted to disrupt the interaction with microtubules. Considering the severe phenotype of our patient, our findings suggest that R3004 may be a key residue for the microtubule-binding affinity of dynein.

KEYWORDS:

DYNC2H1; dynein; microtubule binding; phenotype-genotype correlation; short-rib polydactyly syndrome type III

PMID:
25410398
DOI:
10.1111/cga.12098
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center