Mutations in DYNC2H1 , the cytoplasmic dynein 2, heavy chain 1 motor protein gene, cause short-rib polydactyly type I, Saldino-Noonan type
| Autor: | N Badiner, S P Taylor, Daniel H. Cohn, Michael J. Bamshad, Ralph S. Lachman, Deborah Krakow, Deborah A. Nickerson, K Forlenza |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetics Short rib – polydactyly syndrome Polydactyly Genetic heterogeneity Biology medicine.disease Compound heterozygosity environment and public health Phenotype Ciliopathies 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Micromelia medicine Gene 030217 neurology & neurosurgery Genetics (clinical) |
| Zdroj: | Clinical Genetics. 92:158-165 |
| ISSN: | 0009-9163 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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