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

Autor:	Toshio, Okamoto, Ken, Nagaya, Yumi, Kawata, Hiroko, Asai, Etsushi, Tsuchida, Fumikatsu, Nohara, Kazuki, Okajima, Hiroshi, Azuma
Rok vydání:	2014
Předmět:	Cytoplasmic Dyneins Male Heterozygote Phenotype Mutation Infant Newborn Humans Short Rib-Polydactyly Syndrome
Zdroj:	Congenital anomalies. 55(3)
ISSN:	1741-4520
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::7856843d3a96c4446a5032809b552fbe https://pubmed.ncbi.nlm.nih.gov/25410398 Zobrazit plný text záznamu Plný text