Nephrocalcinosis or nephrolithiasis

Gene: HPRT1

Green List (high evidence)

Should be green, as Lesch-Nyhan syndrome can be associated with urate stones

Created: 30 Oct 2019, 11:59 a.m. | Last Modified: 30 Oct 2019, 11:59 a.m.

Panel Version: 1.23

Comment on list classification: Promoting from red to green. > 3 unrelated cases with variants in this gene and Lesch-Nyhan syndrome with nephrocalcinosis as a feature are reported. Numerous variants are reported. Two publications.

Created: 30 Oct 2019, 2:22 p.m. | Last Modified: 30 Oct 2019, 2:22 p.m.

Panel Version: 1.27

Associated with HPRT-related gout #300323 (XLR) and Lesch-Nyhan syndrome #300322 (XLR) in OMIM, both of which have Nephrolithiasis listed as a clinical feature.

HPRT encodes the Hypoxanthine-guanine phosphoribosyltransferase enzyme. Partial deficiency can result in the overproduction of uric acid leading to a severe form of gout, whilst a virtual absence of HPRT activity causes Lesch-Nyhan syndrome.

PMID: 31129767 - Cho et al 2019 - studied 26 Korean LNS patients from 23 unrelated families. Twenty one of the 23 LNS patients with available data (91.3%) showed renal manifestations such as hyperuricemia, nephrocalcinosis, or urinary stones. 16 patients from 13 families had nephrocalcinosis. Twenty different mutations in HPRT1 were identified from the 23 independent pedigrees.

PMID: 27079129 - Vargiami E et al 2016 - report of two cousins with Lesch-Nyhan syndrome and a confirmed novel HPRT gene mutation: c.65T>C, who both developed nephrocalcinosis and renal failure, findings not been previously published in children with HPRT deficiency.

Created: 19 Oct 2019, 5:28 p.m. | Last Modified: 20 Oct 2019, 1:12 p.m.

Panel Version: 1.20

Mode of inheritance submitted by expert was "XLR", mapping to X-linked recessive = X-LINKED: hemizygous mutation in males, biallelic mutations in females.

Created: 8 Jul 2015, 12:37 p.m.