Amelogenesis imperfecta

Gene: SLC24A4

Comment when marking as ready: Marked as ready: October 19th 2017.

Created: 19 Oct 2017, 9:18 a.m.

Comment on list classification: Updated rating from Red to Green: Green external review, and present on the Leeds diagnostic AI panel. Probable DD-G2P gene (from PMID:23375655, 2 cases) but there are a number of additional papers (PMIDs:24621671, 25442250, 24532815) plus functional studies (e.g. PMID:27129268) with so sufficient (>3) cases for AI causation.

Created: 19 Oct 2017, 9:17 a.m.

PMID:24621671 (2014) identified a homozygous variant (A146V) in SLC24A4 in a 5.5 year old Turkish girl with AI. Her first-cousin parents were heterozygous for the variant.

Created: 19 Oct 2017, 9:07 a.m.

Probable DD-G2P gene for AI based on PMID:23375655 (2013) who identified a homozygous variant in the SLC24A4 gene (R339X) in 3 affected cousins in a consanguineous Pakistani family segregating AI. By Sanger sequencing, they identified another homozygous variant (S499C) in 2 affected cousins in another Pakistani family. The variants were not present in 170 ethnically matched controls, in 70 Gujarati Indian samples, or in VCFs from the 1000 Genomes Project database.

Created: 19 Oct 2017, 9:07 a.m.

Comment on mode of inheritance: Biallelic MOI supported by OMIM.

Created: 19 Oct 2017, 9:01 a.m.

Green List (high evidence)

Currently on the Leeds AI diagnostic panel (Contact: Ruth Charlton). Mutations in SLC24A4 cause a hypomaturation/hypomineralised AI phenotype with autosomal recessive inheritance. Missense mutations affecting both alpha repeats and the cytoplasmic domain, as well as a nonsense mutation and a multi-exonic deletion, have been detected. See SLC24A4 LOVD: http://dna2.leeds.ac.uk/LOVD/genes/SLC24A4

Created: 3 Aug 2017, 2:18 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Amelogenesis imperfecta, type IIA5 615887

Publications

• PMID: 24621671
• 23375655
• 25442250
• 24532815
• 26502894