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

作者：Cossu Carla; Incani Federica; Serra Maria Luisa; Coiana Alessandra; Crisponi Giangiorgio; Boccone Loredana; Rosatelli Maria Cristina^*

来源：Clinica Chimica Acta, 2016, 455: 172-180.

DOI：10.1016/j.cca.2016.02.006

• Jeune syndrome
• short-rib thoracic dystrophies
• whole-exome sequencing
• DYNC2H1
• WDR60

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.

• 出版日期2016-4-1