Amelogenesis imperfecta

Gene: CLDN19

Green List (high evidence)

Comment on list classification: As there are more than 3 unrelated individuals reported in literature with biallelic CLDN19 variants and amelogenesis imperfecta, this gene can be promoted to Green at the next update. However, since the families come from one study, and no other cases have been reported to date, this gene is tagged for expert review regarding strength of evidence.

Created: 5 Jun 2026, 4:56 p.m. | Last Modified: 5 Jun 2026, 4:58 p.m.

Panel Version: 4.36

As reviewed previously by Sarah and Rebecca, there are 6 unrelated families reported in PMID: 27530400 from 2 different ethnic backgrounds. 4 different variants were detected: p.Arg200Gln, p.Gly20Asp, and p.Leu90Arg, p.Gln57*, and p.Gly20Asp (either comp het or homozygous in each proband).

CLDN19:c.599G>A, p.Arg200Gln has MAF = 0.03402 in gnomAD v4.1.1. It is also categorically classified as Benign in ClinVar.
CLDN19:c.59G>A, p.Gly20Asp has MAF = 0.0003840 in gnomAD v4.1. (no homozygotes). Revel score = 0.89 (Moderate).
CLDN19:c.269T>G, p.Leu90Arg is not found in gnomAD v4.1.1. Revel score = 0.96 (Strong).
CLDN19:c.169C>T, p.Gln57* - not in gnomAD v4.1.1.
Thus, 3/4 variants are plausibly P/LP - 5/6 families can be included in the scoring.

CLDN19 is associated with AR Hypomagnesemia 5, renal, with ocular involvement, OMIM:248190 in OMIM (Accessed 5th June 2026). This gene is also Green on the Amelogenesis imperfecta panel in PanelApp Australia.

Created: 5 Jun 2026, 4:54 p.m. | Last Modified: 5 Jun 2026, 4:57 p.m.

Panel Version: 4.36

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hypomagnesemia 5, renal, with ocular involvement, OMIM:248190

Publications

• 27530400

Comment on list classification: Dr Claire E.L. Smith (St James's University Hospital, Leeds, UK) commented that the authors of PMID:27530400 did not carry out any wider genetic analysis on the patients other than direct sequencing of CLDN16 and CLDN19. Given that they have 3 mutations (although one is very common (>1%) in the population) in 6 families this gene should be included on the Amelogenesis Imperfecta panel

Created: 2 Feb 2018, 1:11 p.m.

PMID:27530400 describe 9 patients (6 Brazilian, 3 French) from 6 unrelated families (3 Brazilian, 3 French) with FHHNC carrying homozygous or compound heterozygous CLDN19 mutations: all patients presented AI at different degrees of severity.

Created: 12 Jun 2017, 9:12 a.m.