Prenatal diagnosis of severe mitochondrial diseases caused by nuclear gene defects: a study in Japan

Abstract

Prenatal diagnoses of mitochondrial diseases caused by defects in nuclear DNA (nDNA) or mitochondrial DNA have been reported in several countries except for Japan. The present study aimed to clarify the status of prenatal genetic diagnosis of mitochondrial diseases caused by nDNA defects in Japan. A comprehensive genomic analysis was performed to diagnose more than 400 patients, of which, 13 families (16 cases) had requested prenatal diagnoses. Eight cases diagnosed with wild type homozygous or heterozygous variants same as either of the heterozygous parents continued the pregnancy and delivered healthy babies. Another eight cases were diagnosed with homozygous, compound heterozygous, or hemizygous variants same as the proband. Of these, seven families chose to terminate the pregnancy, while one decided to continue the pregnancy. Neonatal- or infantile-onset mitochondrial diseases show severe phenotypes and lead to lethality. Therefore, such diseases could be candidates for prenatal diagnosis with careful genetic counseling, and prenatal testing could be a viable option for families.

Whose (germ) line is it anyway? Reproductive technologies and kinship

“…Severe mitochondrial diseases caused by defects in either nuclear (nDNA) or mitochondrial DNA (mtDNA) can lead to spontaneous abortion, stillbirth, neonatal, infantile or child death, depending on mutation load and various other factors. 23 Where mtDNA is responsible, this can only be inherited through female gametes as mtDNA is found in the mitochondria (organelles located within the cytoplasm of cells, including the oocyte). Mitochondrial donation from an unaffected woman-using either maternal spindle transfer (MST) or pronuclear transfer (PNT) techniques-can circumvent the issue, allowing the intended mother to pass on her healthy nDNA without her affected mtDNA.…”

Targeting mitochondria in dermatological therapy: beyond oxidative damage and skin aging

“…In addition, mitochondria serve as a hub for an array of vital cellular processes, including ROS-mediated signaling, cell death/survival, calcium homeostasis, fatty acid betaoxidation, fatty acid elongation, heme synthesis, innate immunity, stem cell reprogramming, and heat generation [1,2] (Table 1). Consequently, mitochondrial dysfunction can affect a variety of organ systems, leading to severe pathologies termed ''mitochondrial diseases'', such as neurodegeneration, myopathies, premature aging of the skin and other tissues, and lethality during infancy in the most severe cases [3,4].…”