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.