Title | Mutations in DYNC2H1, the cytoplasmic dynein 2, heavy chain 1 motor protein gene, cause short-rib polydactyly type I, Saldino-Noonan type. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Badiner, N, Taylor, SP, Forlenza, K, Lachman, RS, Bamshad, M, Nickerson, D, Cohn, DH, Krakow, D |
Corporate Authors | University of Washington Center for Mendelian Genomics |
Journal | Clin Genet |
Volume | 92 |
Issue | 2 |
Pagination | 158-165 |
Date Published | 2017 Aug |
ISSN | 1399-0004 |
Keywords | Cytoplasmic Dyneins, Ellis-Van Creveld Syndrome, Female, Fetus, Genetic Heterogeneity, Genetic Predisposition to Disease, Humans, Infant, Newborn, Mutation, Phenotype, Pregnancy, Radiography, Short Rib-Polydactyly Syndrome, Whole Exome Sequencing |
Abstract | The short-rib polydactyly syndromes (SRPS) are autosomal recessively inherited, genetically heterogeneous skeletal ciliopathies. SRPS phenotypes were historically categorized as types I-IV, with type I first delineated by Saldino and Noonan in 1972. Characteristic findings among all forms of SRP include short horizontal ribs, short limbs and polydactyly. The SRP type I phenotype is characterized by a very small thorax, extreme micromelia, very short, poorly mineralized long bones, and multiple organ system anomalies. To date, the molecular basis of this most severe type of SRP, also known as Saldino-Noonan syndrome, has not been determined. We identified three SRP cases that fit the original phenotypic description of SRP type I. In all three cases, exome sequence analysis revealed compound heterozygosity for mutations in DYNC2H1, which encodes the main component of the retrograde IFT A motor, cytoplasmic dynein 2 heavy chain 1. Thus SRP type I, II, III and asphyxiating thoracic dystrophy (ATD), which also result from DYNC2H1 mutations. Herein we describe the phenotypic features, radiographic findings, and molecular basis of SRP type I. |
DOI | 10.1111/cge.12947 |
Alternate Journal | Clin. Genet. |
PubMed ID | 27925158 |
PubMed Central ID | PMC5538819 |
Grant List | R01 DE019567 / DE / NIDCR NIH HHS / United States U54 HG006493 / HG / NHGRI NIH HHS / United States UM1 HG006493 / HG / NHGRI NIH HHS / United States R01 AR066124 / AR / NIAMS NIH HHS / United States R01 AR062651 / AR / NIAMS NIH HHS / United States |