Optic neuropathy

Gene: MT-ND4L

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. The GMS reviewers commented as follows: More appropriate for specialist mitochondrial lab to test for this - 1) Alternative panel test available for this gene (R42.2 - Leber hereditary optic neuropathy). 2). May not be technically feasible for all laboratories to include this gene on the panel.

Created: 11 Dec 2025, 4:54 p.m. | Last Modified: 11 Dec 2025, 4:54 p.m.

Panel Version: 5.28

Green List (high evidence)

Comment on list classification: As reviewed by Katherine Schon, there is sufficient evidence available for the association of m.10663T>C variant from MT-ND4L gene with LHON. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 25 Jun 2025, 4:18 p.m. | Last Modified: 25 Jun 2025, 4:18 p.m.

Panel Version: 5.15

PMID:11935318 - The homoplasmic m.10663T>C variant from MT-ND4L gene has been found in three independent families reported with Leber's hereditary optic neuropathy (LHON), who lack a known primary variant and all of which belong to haplogroup J. However, proband from family B also harboured another missense variant (5244A) and family C harboured 12083G missense variant.

PMID:22879922 - Sequencing of a total of 174 complete mitochondrial genomes was performed in cases highly suspected for LHON, but lacking the three common variants. 16 probands were identified with mitochondrial variants, of which one had m.10663T>C variant. The patient also harboured also a combination of non-synonymous polymorphisms m.8701A>G/MT-ATP6, m.9053G>A/MT-ATP6 and m.10398A>G/MT-ND3.

PMID:29210930 - A 16-year-old boy was reported with LHON and identified with m.10663T>C variant.

PMID:36381806 - A 23-year-old male patient was diagnosed with subacute LHON and with the same m.10663T>C variant.

Created: 25 Jun 2025, 4:16 p.m. | Last Modified: 25 Jun 2025, 4:16 p.m.

Panel Version: 5.12

Mode of inheritance
MITOCHONDRIAL

Phenotypes
Leber hereditary optic neuropathy, MONDO:0010788

Publications

• 11935318
• 22879922
• 29210930
• 36381806

Green List (high evidence)

Rare LHON variants are found in MT-ND4L: m.10663T>C.

Created: 23 Jun 2025, 11:36 a.m. | Last Modified: 23 Jun 2025, 11:36 a.m.

Panel Version: 5.3

Mode of inheritance
MITOCHONDRIAL

Publications

• 29210930
• 36381806