title: Novel compound heterozygous mutations in DYNC2H1 in a patient with severe short-rib polydactyly syndrome type III phenotype.
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.
authors.affiliation: Department of Pediatrics, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Department of Pediatrics, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nagaya
authors.affiliation: Department of Pediatrics, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kawata
authors.affiliation: Department of Pediatrics, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asai
authors.affiliation: Department of Pediatrics, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Etsushi
authors.initials: E
authors.lastname: Tsuchida
authors.affiliation: Department of Pediatrics, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Fumikatsu
authors.initials: F
authors.lastname: Nohara
authors.affiliation: Department of Pediatrics, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Okajima
authors.affiliation: Department of Pediatrics, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Azuma
mesh_terms: D056445:Cytoplasmic Dyneins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012779:Short Rib-Polydactyly Syndrome / Q000235:genetics*
chemical_list: C099883:DYNC2H1 protein, human; D056445:Cytoplasmic Dyneins
keywords: DYNC2H1; dynein; microtubule binding; phenotype-genotype correlation; short-rib polydactyly syndrome type III