Association between maternally inherited deafness, epilepsy, and intellectual disability and the m.12207G > A MT-TS2 pathogenic variant in a Japanese family

Sayaka Suzuki-Ajihara; Megumi Saito-Tsuruoka; Hiroko Harashima; Katsumi Arai; Hiroyoshi Koide; Yukiko Yatsuka; Atsuko Imai-Okazaki; Yasushi Okazaki; Kei Murayama; Chikahiko Numakura; Yuko Akioka; Akira Ohtake

doi:10.1016/j.ymgmr.2023.100966

Association between maternally inherited deafness, epilepsy, and intellectual disability and the m.12207G > A MT-TS2 pathogenic variant in a Japanese family

Mol Genet Metab Rep. 2023 Mar 17:35:100966. doi: 10.1016/j.ymgmr.2023.100966. eCollection 2023 Jun.

Authors

Sayaka Suzuki-Ajihara^{1

2}, Megumi Saito-Tsuruoka^{2

3}, Hiroko Harashima^{1

2}, Katsumi Arai⁴, Hiroyoshi Koide⁴, Yukiko Yatsuka⁵, Atsuko Imai-Okazaki⁵, Yasushi Okazaki⁵, Kei Murayama⁶, Chikahiko Numakura^{1

2}, Yuko Akioka¹, Akira Ohtake^{1

2

3}

Affiliations

¹ Department of Pediatrics, Saitama Medical University, Saitama, Japan.
² Department of Clinical Genomics, Saitama Medical University, Saitama, Japan.
³ Center for Intractable Diseases, Saitama Medical University Hospital, Saitama, Japan.
⁴ Hello Clinic, Saitama, Japan.
⁵ Diagnosis and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
⁶ Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

Abstract

The identification of the m.12207G > A variant in MT-TS2, (NC_012920.1:m.12207G > A) was first reported in 2006. The affected individual presented with developmental delay, feeding difficulty, proximal muscle weakness, and lesions within her basal ganglia, with heteroplasmy levels of 92% in muscle and no evidence of maternal inheritance. Herein, we report a case involving a 16-year-old boy with the same pathogenic variation and different phenotype, including sensorineural deafness, epilepsy, and intellectual disability, without diabetes mellitus (DM). His mother and maternal grandmother had similar but milder symptoms with DM. Heteroplasmy levels of the proband in blood, saliva, and urinary sediments were 31.3%, 52.6%, and 73.9%, respectively, while those of his mother were 13.8%, 22.1%, and 29.4%, respectively. The differences in the symptoms might be explained by the different levels of heteroplasmy. To our knowledge, this is the first familial report of the m.12207G > A variant in MT-TS2 that causes DM. The present case showed milder neurological symptoms than did the former report, and suggests the presence of a good phenotype-genotype correlation within this family.

Keywords: Deafness; Diabetes mellitus; Epilepsy; M.12207G > A MT-TS2; Maternal inheritance.

Publication types

Case Reports