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, 11:44 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

I don't know

This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: CLCN5; Initial rating suggestion: green

Created: 6 Mar 2019, 11:36 a.m.

Comment when marking as ready: Numerous variants reported in these phenotypes.

Created: 13 Jul 2016, 8:07 a.m.

Comment on phenotypes: Variants also reported in: Nephrolithiasis, type I 310468; Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis 308990

Created: 13 Jul 2016, 8:07 a.m.

Comment on list classification: Used diagnostically by Ana Beleza (Guy's and St Thomas' NHS Foundation Trust)

Created: 21 Jun 2016, 12:34 p.m.

Green List (high evidence)

Tier 1

Created: 17 Jun 2016, 8:02 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

Variants in this GENE are reported as part of current diagnostic practice