Leber's hereditary optic neuropathy like disease in MT-ATP6 variant m.8969G>A

Cansu de Muijnck; Mary J van Schooneveld; Astrid S Plomp; Richard J Rodenburg; Maria M van Genderen; Camiel J F Boon

doi:10.1016/j.ajoc.2024.102070

Leber's hereditary optic neuropathy like disease in MT-ATP6 variant m.8969G>A

Am J Ophthalmol Case Rep. 2024 May 3:34:102070. doi: 10.1016/j.ajoc.2024.102070. eCollection 2024 Jun.

Authors

Cansu de Muijnck^{1

2}, Mary J van Schooneveld², Astrid S Plomp^{3

4}, Richard J Rodenburg⁵, Maria M van Genderen^{1

6}, Camiel J F Boon^{2

7}

Affiliations

¹ Department of Ophthalmology, University Medical Center Utrecht, Utrecht, the Netherlands.
² Department of Ophthalmology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
³ Department of Human Genetics, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
⁴ Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands.
⁵ Radboud Center for Mitochondrial Medicine, Departments of Pediatrics and Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
⁶ Bartiméus Diagnostic Center for Complex Visual Disorders, Zeist, the Netherlands.
⁷ Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.

Abstract

Purpose: To describe a case with Leber's hereditary optic neuropathy (LHON) like optic atrophy in the presence of MT-ATP6 gene variant m.8969G > A.

Observations: A 20-year-old patient with a history of mild developmental delay, mild cognitive impairment, and positional tremor presented with subacute painless visual loss over a few weeks. Mitochondrial genome sequencing revealed a variant in MT-ATP6, m.8969G > A (p.Ser148Asn). This variant was previously reported in association with mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) and with nephropathy, followed by brain atrophy, muscle weakness and arrhythmias, but not with optic atrophy.

Conclusions and importance: Rare variants in MT-ATP6 can also cause LHON like optic atrophy. It is important to perform further genetic analysis of mitochondrial DNA in genetically unsolved cases suspected of Leber's hereditary optic neuropathy to confirm the clinical diagnosis.

Keywords: Leber's hereditary optic neuropathy; MT-ATP6; Optic atrophy.

Publication types

Case Reports