Rare Gene Mutations in Romanian Hypoacusis Patients: Case Series and a Review of the Literature

Abstract

(1) Background: In this paper, we report on three cases of hypoacusis as part of a complex phenotype and some rare gene variants. An extensive review of literature completes the newly reported clinical and genetic information. (2) Methods: The cases range from 2- to 11-year-old boys, all with a complex clinical picture and hearing impairment. In all cases, whole exome sequencing (WES) was performed, in the first case in association with mitochondrial DNA study. (3) Results: The detected variants were: two heterozygous variants in the TWNK gene, one likely pathogenic and another of uncertain clinical significance (autosomal recessive mitochondrial DNA depletion syndrome type 7—hepatocerebral type); heterozygous variants of uncertain significance PACS2 and SYT2 genes (autosomal dominant early infantile epileptic encephalopathy) and a homozygous variant of uncertain significance in SUCLG1 gene (mitochondrial DNA depletion syndrome 9). Some of these genes have never been previously reported as associated with hearing problems. (4) Conclusions: Our cases bring new insights into some rare genetic syndromes. Although the role of TWNK gene in hearing impairment is clear and accordingly reflected in published literature as well as in the present article, for the presented gene variants, a correlation to hearing problems could not yet be established and requires more scientific data. We consider that further studies are necessary for a better understanding of the role of these variants.

Characteristics of Developmental and Epileptic Encephalopathy Associated with PACS2 p.Glu209Lys Pathogenic Variant—Our Experience and Systematic Review of the Literature

“…PACS2 encodes a multifunctional sorting protein that plays a vital role in pathway traffic regulation [ 7 , 39 ], ion channel trafficking, nuclear gene expression [ 41 ], autophagy, and apoptosis [ 10 , 12 , 42 ]. The missense variant G.625>A (p.Glu209Lys) in the PACS2 gene is associated with phenotypic traits that partially overlap with the PACS1-related phenotype [ 7 ].…”

“…PACS2 encodes a multifunctional sorting protein that plays a vital role in pathway traffic regulation [7,39], ion channel trafficking, nuclear gene expression [41], autophagy,…”

Defining the URCOTEBS System as a Unilateral Radiographic–Stochastic Model for the Complementary States (Health/Disease) of the D-Organ and Middle-Ear Mucosa

“…Middle-ear pathology leading to hearing loss is the most serious problem confronting the otologist, as the WHO estimates that between 65 and 330 million individuals suffer from some form of middle ear suppuration and that 50% of them suffer from hearing impairment, which could also be caused by a number of clinical and environmental factors [11][12][13]. The middle-ear or tympanic cavity is a very complicated structure, with notoriously intricate small-sized segments geometrically arranged as irregular interlinked spheroidal and polyhedric cavities.…”

Materials for ossicular chain reconstruction: History and evolution (Review)

“…the integrity of the auditory system is one of the prerequisites for the acquisition and proper development of oral language. an individual suffering from hypoacusis is more likely to have poorer professional results than his colleagues, will be less competitive in the labor market and will have less chances to complete a higher education (2,3). Etiologically, hearing loss is defined as having two main mechanisms: Conductive hearing loss (CHl) following the pathology of the external and middle ear with air-conduction impairment and sensorineural hearing loss following inner ear pathology with bone-conduction impairment.…”