Skeletal dysplasia
Gene: CLCN5
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 LesterCreated: 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
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: greenCreated: 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 308990Created: 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.
Tier 1Created: 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
Added phenotypes Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis 308990; Dent disease 300009; Nephrolithiasis, type I 310468; Hypophosphatemic rickets 300554 for gene: CLCN5
Source NHS GMS was added to CLCN5. Rating Changed from Green List (high evidence) to Green List (high evidence)
Promoted to version 1 9th August 2016
This gene has been classified as Green List (High Evidence).
Phenotypes for CLCN5 were set to Dent disease 300009; Hypophosphatemic rickets 300554; Nephrolithiasis, type I 310468; Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis 308990
Mode of inheritance for CLCN5 was changed to X-LINKED: hemizygous mutation in males, biallelic mutations in females
This gene has been classified as Green List (High Evidence).
CLCN5 was added to Unexplained skeletal dysplasiapanel. Source: Emory Genetics Laboratory CLCN5 was added to Unexplained skeletal dysplasiapanel. Source: Expert Review Red
CLCN5 was added to Unexplained skeletal dysplasiapanel. Sources:
CLCN5 was created by sleigh