Structural eye disease

Gene: ALX1

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 2 May 2024, 1:56 p.m. | Last Modified: 2 May 2024, 1:56 p.m.

Panel Version: 3.79

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 29 Sep 2023, 2:12 p.m. | Last Modified: 29 Sep 2023, 2:12 p.m.

Panel Version: 3.21

ALX1 variants have been associated with Frontonasal dysplasia 3 (OMIM:613456) and as definitive Gen2Phen gene for the same condition. At least four ALX1 variants have been reported. Extreme microphthalmia and severe facial clefting was seen in three sibling carrying a 3.7 Mb deletion containing the ALX1 gene (PMID: 20451171). Microphthalmia and other clefting defects we observed in a case with biallelic ALX1 variant c.531-1G>A (PMID: 20451171). PMID: 32914578 reported a family with four siblings who were biallelic for ALX1 c.493C>T (p.F165F). Three of these cases were anophthalmic and the fourth case had coloboma. Supportive functional studies are presented by PMID: 23059813 & 32914578.

Created: 29 Sep 2023, 2:11 p.m. | Last Modified: 29 Sep 2023, 2:11 p.m.

Panel Version: 3.20

Green List (high evidence)

Additional paper (PMID: 32914578) reported an Amish family with four affected children, with a homozygous missense mutation. All four had bilateral oblique facial clefts and ocular abnormalities - one with bilateral coloboma and asymmetric microphthalmia, and three with bilateral anophthalmia

Created: 12 Sep 2023, 11:09 a.m. | Last Modified: 12 Sep 2023, 11:09 a.m.

Panel Version: 3.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Frontonasal Dysplasia 3

Publications

• 32914578

I don't know

Uz reported two unrelated families, one with three siblings affected by frotonasal dysplasia including bilateral severe microphthalmia harbouring a 3.5mb homozygous deletion including ALX1 present in all three siblings and in heterozygous state in parents and another child with frontonasal dysplasia including bilateral microphthalmia harbouring a homozygous splice site variant present in heterozygous state in parents. Dee reported zebrafish model.

Created: 2 Oct 2019, 3:48 p.m. | Last Modified: 2 Oct 2019, 3:48 p.m.

Panel Version: 0.91

Publications

• 20451171
• 23059813

Green List (high evidence)

Phenotypes
Frontonasal Dysplasia 3, FND3