Nephrocalcinosis or nephrolithiasis

Gene: PHEX

Green List (high evidence)

PHEX (phosphate regulating endopeptidase homolog X-linked)
EnsemblGeneIds (GRCh38): ENSG00000102174
EnsemblGeneIds (GRCh37): ENSG00000102174
OMIM: 300550, Gene2Phenotype
PHEX is in 7 panels

2 reviews

Detlef Bockenhauer (GOSH-UCL)

Green List (high evidence)

Add this gene.
Created: 30 Oct 2019, 11:59 a.m. | Last Modified: 30 Oct 2019, 11:59 a.m.
Panel Version: 1.23

Eleanor Williams (Genomics England Curator)

Comment on list classification: In light of expert review and consultation with the Genomics England clinical team it was decided to promote this gene from red to green. >3 cases reported with variants in this gene in patients with nephrocalicinosis.
Created: 6 Nov 2019, 4:28 p.m. | Last Modified: 6 Nov 2019, 4:28 p.m.
Panel Version: 1.43
Comment on mode of inheritance: Following XLD mode of inhertiance in OMIM, so changing to X-Linked: hemizyous mutation in males, monoallelic in females. Monoallelic variants causing disease in females are reported e.g. PMID: 10439971 Filisetti et al 1999
Created: 30 Oct 2019, 3:37 p.m. | Last Modified: 6 Nov 2019, 4:26 p.m.
Panel Version: 1.42
Personal communication from Detlef Bockenhauer. They see nephrocalcinosis in ~50% patients. It clearly is also related to treatment, but probably an intrinsic part of the disease.
Created: 30 Oct 2019, 2:26 p.m. | Last Modified: 30 Oct 2019, 2:26 p.m.
Panel Version: 1.27
Associated with Hypophosphatemic rickets, X-linked dominant (#307800)(XLD) in OMIM.

PMID: 31514490 - Şıklar et al 2019 - Study of 166 patients with Hypophosphatemic rickets from 24 centers in Turkey. Genetic analysis (n:75) showed PHEX mutation in 80% patients (60 patients). 27 patients developed nephrocalcinosis. However, higher treatment dose of phosphate and calcitriol has been detected in nephrocalcinosis group.

PMID: 29460029 - Chesher et al 2018 - clinical records of 59 adult patients from 35 kindreds with X-linked hypophosphatemia attending a single inherited metabolic disease service from 1998 were retrospectively reviewed. All had PHEX mutations (either directly obtained or inferred from the result of a first degree relative). 37 distinct variants were identified (14 not previously reported). Nephrocalcinosis was reported in 16/38 patients (42%) with at least one renal ultrasound performed. Treatment with vitamin D was associated with a small increase in urine calcium but there was no association between the presence or absence of nephrocalcinosis and whether or not the patient was currently being treated with vitamin D.

Will consult with Genomics England Clinical team with regards to nephrocalcinosis being associated with PHEX variants or a result of treatment for Hypophosphatemic rickets.
Created: 21 Oct 2019, 12:17 a.m. | Last Modified: 21 Oct 2019, 4:46 a.m.
Panel Version: 1.22

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • Literature
  • Expert list
Phenotypes
  • Hypophosphatemic rickets, X-linked dominant 307800
OMIM
300550
Clinvar variants
Variants in PHEX
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Nov 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: phex has been classified as Green List (High Evidence).

6 Nov 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: PHEX were set to

6 Nov 2019, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: PHEX were changed from to Hypophosphatemic rickets, X-linked dominant 307800

30 Oct 2019, Gel status: 1

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: PHEX was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

20 Oct 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Eleanor Williams (Genomics England Curator)

gene: PHEX was added gene: PHEX was added to Nephrocalcinosis or nephrolithiasis. Sources: Expert list,Literature Mode of inheritance for gene: PHEX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females