Abstract
We reported a delayed diagnosised Chinese JATD case with mild skeletal phenotype, and presented with renal insufficiency as the initial symptom of disease onset. Novel bilateral c.2789C>T (p.S930L) mutations in WDR60 gene were identified. Our report will help to improve our awareness and diagnosibility for this disease in China.
Key clinical message
This JATD case presented with atypical skeletal anomalies , chronic renal failure was the initial symptom of the disease onset, easily resulting in an error diagnosis .
Key words: Jeune asphyxiating thoracic dystrophy; WDR60 gene; ciliopathyies; skeletal ciliopathyies; renal failure
Introduction
Primary cilium is an immotile microtubule-based structure that protrudes from the cell surface and distributes in almost all vertebrate cell types. In cell, cilium acts as an antenna and plays a pivotal role in chemical sensation, signal transduction, and control of organogenesis[1, 2, 3, 4].
Defects in the assembly and functions of cilia result in a variety of congenital disorders, known as ciliopathyies, characterized by the high heterogeneity of clinical manifestations. Ciliopathyies could involve most major tissues and organs and cause a broad spectrum of phenotypes including skeletal malformations and retinal degeneration, polycystic kidney, polydactyly, infertility, morbid obesity and mental retardation[5, 6, 7, 8].
Jeune asphyxiating thoracic dystrophy (JATD; MIM 208500) was first described in 1955[9], and characterized by skeletal anomalies, primarily shortened ribs and limbs, brachydactyly and variable polydactyly. The estimated incidence of this disease is about 1 in 100,000 live births[10]. JATD belongs to the ciliopathy diseases spectrum- skeletal ciliopathies. In addition to JATD, skeletal ciliopathies also encompass short-rib polydactyly syndromes (SRPS; MIM 611263, MIM613091, MIM 263520, MIM 269860, MIM 614091), Mainzer-Saldino syndrome (MZSDS; MIM 266920)[11], Sensenbrenner syndrome or cranio-ectodermal dysplasia (CED; MIM 218330)[12], oral-facial-digital syndrome 4 (OFD4; MIM 258860) and Ellis-van Creveld syndrome (EVC; MIM 225500)[10, 12, 13]. Apart from distinctive skeletal changes, these diseases often give rise to the involvement of extraskeletal organs, and cause extraskeletal phenotypes including polycystic kidney disease, retinal degeneration, and cardiac, liver, and brain anomalies[6, 14].
By far, it has been established a causative link between JATD and mutations in dozens of genes that all involved in the assembly and transport of cilia[13, 15, 16]. The association of WDR60 gene with ciliopathies was recognized for the first time in 2013[17]. WD60 protein acts as a dynein intermediate chain required for retrograde intraflagellar transport in cilia[18, 19]. mutations of WDR60 can cause both SRPS and JATD phenotypes, So far, 5 mutations have been identified and no case has been report in Chinese population [13, 17, 20]. Here, we describe a delayed diagnosis Chinese JATD case with moderate degree of skeletal phenotype and renal insufficiency as the initial symptom of disease onset. Novel bilateral c.2789C>T (p.S930L) mutations in WDR60 gene were identified from the patient and confirm the mutation co-segregation in the family. This report will expand the phenotypic spectrum caused by WDR60 mutations and contribute to improving our awareness and diagnosability for this disease in China.