Molecular and hereditary mechanisms of sensorineural hearing loss with focus on selected endocrinopathies

Abstract

Hearing loss is one of the most widespread sensory disorders. The incidence of deafness in general population is 1:1000 newborns. About one half of the congenital sensorineural hearing loss (SNHL) cases is inherited. Recessive mutations in the gap junction beta 2 (GJB2) gene are the most common genetic causes of the nonsyndromic SNHL. The GJB2 encodes a protein connexin 26 which forms a subunit of gap junction essential for the correct function of the inner ear. The syndromic SNHL is associated with a wide range of other symptoms, which encompass also dysfunctions of endocrine organs. The Pendred syndrome associated with the hearing impairment is characterized by a prelingual, bilateral sever to profound SNHL, goiter, and iodine organification defect. It is an autosomal recessive disorder, which develops due to mutations in pendrin, an anion channel encoded by SLC26A4 gene. Another important type of syndromic hearing loss is the Maternally Inherited Diabetes and Deafness syndrome, which is caused by several mitochondrial DNA mutations. These mutations are clinically manifested by a hearing impairment with development of the diabetes in the adult age. Hearing impairment occurs during puberty when sensation of high frequency tones is affected following with further progress to profound bilateral sensorineural hearing impairment in the whole frequency range. This review deals with the molecular mechanisms of common genetic causes of the hereditary SNHL along with the selected endocrinopathies emphasizing that the DNA analyses along with the functional studies significantly contribute to the early SNHL diagnosis followed by personalized therapy and genetic counseling. sensorineural hearing lossHearing loss is one of the most common sensory disorders. Based on the World Health Organization's data, over 278 million people suffer from the hearing loss (WHO 2010). The incidence of profound hearing loss is 1:1000 in newborns (Morton 1991); however, the etiology of the hearing disorders is extremely diverse. Approximately half of the congenital sensorineural hearing loss (SNHL) is caused by genetic abnormalities, 25% by environmental factors, and the remaining 25% has unknown origin (Morton 1991; Schrijver 2004).

Genetics of Hearing Loss

“…In addition to SNHL, patients who suffer from this syndrome also show features of congenital and severe to profound temporal bone abnormalities, in addition to goiter partial iodine organification defects resulting in a positive perchlorate discharge test from the goiter, usually in late childhood to early adulthood. Pendred syndrome also features thyroid dysfunction, ranging from euthyroid to hypothyroidism 56, 57 , and vestibular dysfunction, demonstrated in approximately 65% of affected individuals. The vestibular dysfunction can range from mild unilateral canal paresis to gross bilateral absence of function 58 .…”

Caratterizzazione della mutazione SLC26A4 c.918+2T>C e report di una nuova variante potenzialmente a rischio

“…It is comprised of 780 amino acids and is predicted to have 12 putative transmembrane domains, with both the amino- and carboxy-termini located on the cytosol 13 14 . In the C-terminus region a STAS domain (Sulfate Transporter Antagonist of Anti-Sigma Factor) is located,which probably plays an important role in the biosynthesis, function and regulation of this transporter 15 16 . The SLC26A4 gene is expressed in specific areas of the endolymphatic compartment in the cochlea known to play a role in the endolymph reabsorption 17 .…”

Relationship Metabolic Syndrome and Hearing Loss: Review of Literature

“…16,17 İlginç olarak yüksek frekans sensörinöral işitme kaybı ile DM arasında ilişki vardır. 18,19 MetS; HT, hipertrigliseridemi, glukoz intoleransı, santral obezite ve düşük HDL komponentlerinden oluşur. Bu durum kardiyovasküler hastalık, KAH ve DM oluşum risklerinde artış ve mortalitenin her türlü nedeni ile ilişkilidir.…”

“…Bu durum kardiyovasküler hastalık, KAH ve DM oluşum risklerinde artış ve mortalitenin her türlü nedeni ile ilişkilidir. 10,[16][17][18][19][20] Bugüne kadar işitme kaybı ile MetS arasında doğrudan bir ilişkiyi araştıran çok az çalışma yapılmıştır: Zhao ve ark., 165 vaka ile yaptıkları çalışmada, MetS bileşenlerinden TG yüksekliği ile yaşa bağlı işitme kaybı arasında ilişki olduğunu saptamışlardır. Ek olarak, MetS bileşenlerinin tüm kombinasyonları arasında, TG ve HDL kolesterol kombinasyonu, TG ve kan şekeri kombinasyonu, TG ve kan basıncı kombinasyonu yaş ilişkili işitme kaybı ile korele bulunmuştur.…”