New mutations in DYNC2H1 and WDR60 genes revealed by whole-exome sequencing in two unrelated Sardinian families with Jeune asphyxiating thoracic dystrophy

• Published in: Clinica chimica acta 2016-04, Vol.455, p.172-180
• Main Authors: Cossu, Carla, Incani, Federica, Serra, Maria Luisa, Coiana, Alessandra, Crisponi, Giangiorgio, Boccone, Loredana, Rosatelli, Maria Cristina
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Cytoplasmic Dyneins - genetics; DYNC2H1; Ellis-Van Creveld Syndrome - genetics; Female; Humans; Italy; Jeune syndrome; Male; Mutation; Pedigree; short-rib thoracic dystrophies; WDR60; whole-exome sequencing
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2016.02.006

Jeune asphyxiating thoracic dystrophy (JATD; Jeune syndrome, MIM 208500) is a rare autosomal recessive chondrodysplasia, phenotypically overlapping with short-rib polydactyly syndromes (SRPS). JATD typical hallmarks include skeletal abnormalities such as narrow chest, shortened ribs, limbs shortened bones, extra fingers and toes (polydactyly), as well as extraskeletal manifestations (renal, liver and retinal disease). To date, disease-causing mutations have been found in several genes, highlighting a marked genetic heterogeneity that prevents a molecular diagnosis of the disease in most families. Here, we report the results of whole-exome sequencing (WES) carried out in four JATD cases, belonging to three unrelated families of Sardinian origin. The exome analysis allowed to identify mutations not previously reported in the DYNC2H1 (MIM 603297) and WDR60 (MIM 615462) genes, both codifying for ciliary intraflagellar transport components whose mutations are known to cause Jeune syndrome. •Whole-exome sequencing (WES) was carried out in three unrelated Sardinian families•We identified mutations not previously reported in DYNC2H1 and WDR60 genes•WES is an efficient technology for molecular diagnosis of genetic heterogeneous diseases