Retinal disorders

Gene: MPDZ

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, 1:45 p.m. | Last Modified: 2 May 2024, 1:45 p.m.

Panel Version: 5.2

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There are five unrelated cases and supporting functional evidence available for the association of this gene with this panel and hence this gene can be promoted to green rating at the next GMS review.

Created: 4 Aug 2023, 7:50 p.m. | Last Modified: 4 Aug 2023, 7:50 p.m.

Panel Version: 4.23

PMID:28556411 - Three unrelated patients were reported with biallelic MPDZ variants and congenital hydrocephalus and eye/ brain anomalies. The 2.5 year-old with homozygous variant (p.Gln1490Argfs*19) had macular hypoplasia, 8 year-old boy with compound heterozygous variants (p.Arg744Ter & p.Arg1071Ter) had foveal dysplasia with thin inner retina, and 15-month old boy with homozygous variant (p.Ala1760Thr) had iris coloboma and prominent optic nerve. This 15-month old boy also had cholestasis and liver failure associated with a variant in the TJP2 gene (p.[Leu192Profs*3]).

PMID:36429029 - A Chinese proband with isolated bilateral macular coloboma was identified with compound heterozygous variants (p.Asp1434fs*3 & p.Ser1752Ter). In addition, results from in silico analysis and phenotypes observed in zebrafish knockdown model recapitulate the phenotypes observed in the proband.

PMID:36594712 - A 4 year-old proband presenting with intermittent exotropia and decreased vision in both eyes was identified with compound heterozygous variants in MPDZ gene (c.3100C>T/ p.Arg1034Ter & c.747 + 2T>G). This patient had macular colobomas and far temporal chorioretinal atrophy in both eyes. His 9 year-old older brother with the same variants had a visual acuity of 20/25 in the right eye and 20/40 in the left eye and was found to have subtle changes in the foveal reflex of both eyes.

This gene has been associated with relevant phenotypes in OMIM (MIM #615219), which included the clinical manifestations associated with eyes.

Created: 4 Aug 2023, 7:44 p.m. | Last Modified: 4 Aug 2023, 7:44 p.m.

Panel Version: 4.20

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hydrocephalus, congenital, 2, with or without brain or eye anomalies, OMIM:615219

Publications

• 28556411
• 36429029
• 36594712

PMID 28556411: 3 families with affected individuals with biallelic MPDZ variants and congenital hydrocephalus with retinohoroidal coloboma, macular hypoplasia and foveal hypoplasia
PMID 36594712: 2 siblings with biallelic MPDZ variants and macular colobomas
PMID 36429029: proband with biallelic MPDZ variants and macular coloboma
Sources: Literature

Created: 28 Jul 2023, 6:44 p.m. | Last Modified: 28 Jul 2023, 6:44 p.m.

Panel Version: 4.20

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• PMID 28556411, 36594712, 36429029

Mode of pathogenicity
Other