Mutations in DYNC2H1, the cytoplasmic dynein 2, heavy chain 1 motor protein gene, cause short-rib polydactyly type I, Saldino-Noonan type.
Clin Genet
; 92(2): 158-165, 2017 Aug.
Article
in En
| MEDLINE
| ID: mdl-27925158
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Short Rib-Polydactyly Syndrome
/
Ellis-Van Creveld Syndrome
/
Genetic Predisposition to Disease
/
Cytoplasmic Dyneins
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Female
/
Humans
/
Newborn
/
Pregnancy
Language:
En
Journal:
Clin Genet
Year:
2017
Document type:
Article
Affiliation country:
United States