Mutational screening in patients with profound sensorineural hearing loss and neurodevelopmental delay: Description of a novel m.3861A > C mitochondrial mutation in the MT-ND1 gene

Previously Unreported Biallelic Mutation in DNAJC19: Are Sensorineural Hearing Loss and Basal Ganglia Lesions Additional Features of Dilated Cardiomyopathy and Ataxia (DCMA) Syndrome?

“…Sensorineural deafness, visual loss, intellectual disability, and movement disorders are the main components of this progressive neurodegenerative disorder (Tranebjaerg et al 1995). Deafness is also found in another inborn error of metabolism with 3-MGAuria as a discriminating feature (SERAC1 defect (Wortmann et al 2012)) and is frequently seen in mitochondrial disorders (Ammar et al 2016) which could indicate that it is a part of the clinical spectrum of DNAJC19 defect. Alternatively, isolated hearing loss is a frequent finding and could also be due to a second (genetic) disorder.…”

Mitochondrial complex I subunit MT-ND1 mutations affect disease progression

“…MT-ND1 mutations might also cause hearing impairment and cardiovascular diseases, such as cardiomyopathy and hypertension. Mutation m.3861 A > C/ND1 is associated with syndromic hearing loss [ 63 ]. Mutation m.3395 A > G/MT-ND1 leads to a decrease in the MT-ND1 protein level and a decrease in CI activity and level [ 64 ], and this mutation was also found in patients with hypertrophic cardiomyopathy and severe bilateral hearing loss, which may have cumulative negative effects on cardiac function [ 65 ].…”

A Consolidated Understanding of the Contribution of Redox Dysregulation in the Development of Hearing Impairment

“…An examination of the novel involvement in these genetic factors in parts of the redox pathway (Table 1, column on the speculated involvement in redox homeostasis) provides a plausible direction for future research investigating the relationship between the loss of auditory protein function, susceptibility to hearing loss, and cellular redox imbalance, particularly in the absence of cellular loss. More importantly, genetic factors with direct involvement in mitochondria function (MTCO1 cytochrome c oxidase subunit 1 and MTND1 reduced nicotinamide adenine dinucleotide (NADH)-ubiquinone oxidoreductase chain 1) [99,100], ROS production (ClpP caseinolytic mitochondrial matrix peptidase proteolytic subunit, NLRP3 nucleotidebinding domain, leucine-rich-containing family, and pyrin domain-containing-3) [101,102], development of oxidative stress (HSD17B4 17-β-hydroxysteroid dehydrogenase and WFS1 wolframin endoplasmic reticulum transmembrane glycoprotein) [103,104], and apoptosis (AIFM1 apoptosis-inducing factor and mitochondria-associated 1) [105] link activitydependent cellular alterations with redox imbalance and pathology of the auditory tissues.…”