Nephrocalcinosis or nephrolithiasis

Gene: FAM20A

Green List (high evidence)

Should be green. It is now recurrently reported to cause NC, albeit an unusual form (cortical rather than medullary).

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: Upgrading from red to green. 3 independent cases where nephrocalcinosis is reported plus mouse knockout data showing a renal phenotype.

Created: 6 Nov 2019, 4:09 p.m. | Last Modified: 6 Nov 2019, 4:09 p.m.

Panel Version: 1.40

Associated with Amelogenesis imperfecta, type IG (enamel-renal syndrome) (#204690)(AR) in OMIM and AMELOGENESIS IMPERFECTA AND GINGIVAL FIBROMATOSIS SYNDROME (confirmed, biallelic) in Gene2Phenotype.

PMID: 23468644 - Wang et al 2013 - Characterized three families (from the Caribbean, Jordan and Iran) with amelogenesis imperfecta and gingival fibromatosis syndrome (AIGFS) and identified, in each case, recessive FAM20A mutations with different variants in each family. Significantly, a kidney ultrasound of the family 2 proband revealed nephrocalcinosis, revising the diagnosis from AIGFS to Enamel-renal syndrome. Ultrasounds were not possible to obtain from families 1 and 3.

PMID: 30394349 - Dourado et al 2018 - investigated ERS characteristics in 11 patients from 5 Brazilian families.
All showed hypoplastic amelogenesis imperfecta, microdontia, intra-pulpal calcification, impacted posterior teeth with hyperplastic pericoronal follicles, gingival fibromatosis, ectopic calcifications on gingival and pericoronal tissues, and nephrocalcinosis. A biallelic loss of function variant in FAM20A [NG_029809.1: c.1447delG; p.(Glu483Lysfs*24)], was detected in all patients, strongly suggesting a founder effect.

PMID: 28298625 - Kantaputra et al 2017 (Abstract only accessed) - report three patients and their families with findings suggestive of Enamel-renal-gingival syndrome. Mutation analysis of FAM20A was performed in all patients and their family members. Patients with homozygous frameshift and compound heterozygous mutations in FAM20A had typical clinical findings along with periodontitis. The other had a novel homozygous missense mutation in exon 10, mild gingival fibromatosis and renal calcifications.

PMID: 22732358 - Vogel et al 2012 - two-thirds of Fam20a–/– mice had small kidneys with pitted surfaces, which showed widespread calcification (as well as a dental phenotype)

3 independent cases with nephrocalcinosis plus mouse knockout data. Not full penetrance for the renal phenotype.

Created: 17 Oct 2019, 10:28 p.m. | Last Modified: 17 Oct 2019, 10:28 p.m.

Panel Version: 1.18