The first Korean cases of combined oxidative phosphorylation deficiency 35 with two novel TRIT1 mutations in two siblings confirmed by clinical and molecular investigation

A Case of Combined Oxidative Phosphorylation Deficiency 35 Associated with a Novel Missense Variant of the <b><i>TRIT1</i></b> Gene

“…The main clinical manifestations were febrile and/or myoclonic seizures, microcephaly, developmental delay, intellectual disability, failure to thrive, vision problems, and EEG abnormalities (Table 1). Moreover, cardiac involvement, polyuria-polydipsia, endocrinopathies such as elevated TSH and diabetes, skin abnormalities, structural brain anomalies, and biochemical abnormalities were detected less frequently [Yarham et al, 2014;Kernohan et al, 2017;Takenouchi et al, 2019;Yoo et al, 2021]. Abnormal neuroimaging findings such as cerebral atrophy, mega cisterna magna, Dandy-Walker syndrome, hydrocephalus, septo-optic dysplasia, and partial agenesis of the corpus callosum have been reported in patients with COXPD35 [Kernohan et al, 2017;Yoo et al, 2021].…”

“…To date, only 10 types of allelic variants in TRIT1 gene have been previously reported in 9 patients with COXPD35 (Table 1) [Yarham et al, 2014;Kernohan et al, 2017;Takenouchi et al, 2019;Yoo et al, 2021]. The onset of symptoms occurs in early infancy (range 3-13.5 months).…”

“…There are many subtypes and genotypic/phenotypic heterogeneity. Combined oxidative phosphorylation deficiency 35 (COXPD35; OMIM #617873) is a rare autosomal recessive disorder associated with homozygous or compound heterozygous mutations in the tRNA isopentenyltransferase (TRIT1) gene in chromosome 1p34.2 [Yarham et al, 2014;Kernohan et al, 2017;Takenouchi et al, 2019;Yoo et al, 2021].…”

TRIT1 defect leads to a recognizable phenotype of myoclonic epilepsy, speech delay, strabismus, progressive spasticity, and normal lactate levels

“…It would be of great interest to facilitate connecting families to researchers/clinicians having interest for TRIT1 functional characterization and natural history. experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.…”

“…Including our two novel patients (see Supporting Information), 15 patients have been described in the medical literature so far (five males, eight females, for two patients, the gender was not reported 1,[3][4][5][6][7][8][9] ). Age of symptom onset was between 3 and 14 months, and one patient had symptom onset antenatally (for four patients, age of symptom onset was not reported).…”