Amelogenesis imperfecta

Gene: PEX26

Green List (high evidence)

The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 5:04 p.m. | Last Modified: 1 Feb 2023, 5:04 p.m.

Panel Version: 2.22

Comment on list classification: Leaving rating as amber for now, but with recommendation for green rating following GMS review. 3 cases now reported with a syndromic amelogenesis imperfecta phenotype.

Created: 19 Aug 2021, 12:56 p.m. | Last Modified: 19 Aug 2021, 12:56 p.m.

Panel Version: 2.14

As reported by Zornitza Stark, PMID:33926089 (Kim et al 2021) describes an 8 year old boy with amelogenesis imperfecta in permanent dentition as well as sensorineural hearing loss. WES of the patient and parents identified a homozygous mutation (c.506T>C, p. (Leu169Pro)) in the PEX26 gene. The mother and father were both asymptomatic carriers.

Created: 19 Aug 2021, 12:52 p.m. | Last Modified: 19 Aug 2021, 12:52 p.m.

Panel Version: 2.11

Green List (high evidence)

Third family reported with Heimler syndrome phenotype, including amelogenesis imperfecta.

Created: 13 Aug 2021, 1:29 a.m. | Last Modified: 13 Aug 2021, 1:29 a.m.

Panel Version: 2.8

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Heimler syndrome

Publications

• 33926089

Comment on phenotypes: At the time of curation, PEX26 is not yet linked to Heimler syndrome in OMIM.

Created: 23 Oct 2017, 12:35 p.m.

Comment on list classification: Updated rating from Grey to Amber: PEX26 was added to panel and rated Green by Claire Smith. Only 2 cases reported so far (PMID:28944237 and see Claire's review) so rated as Amber with 'watchlist' tag awaiting further cases.

Created: 23 Oct 2017, 12:32 p.m.

PMID:28944237 report 2 patients from 2 families diagnosed with 'Usher syndrome with additional abnormalities' with compound heterozyous PEX26 mutations. Both patients (a 14 year old boy, and a 4 year old girl) displayed enamel defects on deciduous teeth. The boy had amelogenesis imperfecta on permanent teeth. This is the first evidence linking PEX26 to Heimler syndrome.

Created: 23 Oct 2017, 12:24 p.m.

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

Created: 23 Oct 2017, 11:55 a.m.

Green List (high evidence)

PEX26 forms part of a complex with PEX1 and PEX6 and therefore has been a strong candidate gene for Heimler syndrome and therefore also syndromic amelogenesis imperfecta. Patients with PEX1 and PEX6 variants are often misdiagnosed with deafness or with Usher syndrome type II. Investigation of the enamel can discern Heimler syndrome from other syndromes of deaf-blindness. Two families with AI (as part of Heimler syndrome) and with PEX26 variants have been reported to date.

Created: 20 Oct 2017, 2:09 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
614872 Peroxisome biogenesis disorder 7A (Zellweger); 614873 Peroxisome biogenesis disorder 7B

Publications

• PMID:28944237