GMS Musculoskeletal specialist test group Skeletal dysplasia

Gene: CLCN5

Green List (high evidence)

300554 listed in Abnormal mineralization gp of SD. XLR. Same variant reported in 2 families with differing severity of phenotype (S244L) - OMIM. A further case reported by Guven et al 2017 has a truncating variant. Other disorders not listed in SD nosology paper, although Dent's disease also has rickets and short stature? S244L has also been reported in association with Dent's without rickets (eg Hoopes et al 1998, Tang et al 2016). Functional studies suggest S244L. abolishes anion conductance sequence (Tang et al 2016). Green/amber for 300554?; Review on behalf of Tracy Lester

Created: 6 Mar 2019, 11:52 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Dent disease 300009; Hypophosphatemic rickets 300554; Nephrolithiasis, type I 310468; Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis 308990