Genetic epidemiological studies of early‐onset deafness in the U.S. school‐age population

Marazita, Mary L.; Ploughman, Lynn; Rawlings, Brenda W.; Remington, Elizabeth; Arnos, Kathleen S.; Nance, Walter E.

doi:10.1002/ajmg.1320460504

Cited by 412 publications

(301 citation statements)

References 2 publications

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“…1 Genetic causes of hearing loss are quite heterogeneous and to date 42 genes associated with non-syndromic hearing loss have been identified (http://webhost.ua.ac.be/hhh/). Among them, connexin 26 (Cx26 or GJB2) is the major known cause of hearing loss in Europe, 2 -4 the United States 5 and Japan.…”

Section: Introductionmentioning

confidence: 99%

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss

et al. 2008

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In a study of 530 individuals with non-syndromic, sensorineural hearing loss, we identified 18 mutations at connexin 26 (Cx26), four of which are novel (À23G4T, I33T, 377_383dupTCCGCAT, W172R) and the remaining 14 (ivs1 þ 1G4A, M1V, 35delG, W24X, I35S, V37I, R75W, W77X, 312del14, E120del, Q124X, Y136X, R143W, R184P) being mutations previously described. To gain insight into functional consequences of these mutations, cellular localization of the mutant proteins and their ability to permit lucifer yellow transfer between cells was studied in seven of them (W24X, I33T, I35S, R75W, E120del, W172R and R184P). I35S and R184P showed impaired trafficking of the protein to the plasma membrane. I33T, R75W, E120del and W172R showed predominantly membrane localization but did not form functional gap junction channels. Surprisingly, W24X, a protein-truncating mutation, apparently permits formation of a full-length protein, perhaps due to a stop codon read-through mechanism. These results provide further evidence that Cx26 mutations affect gap junction activity by mis-regulation at multiple levels.

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Section: Introductionmentioning

confidence: 99%

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss

et al. 2008

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“…More than 50% of these cases are hereditary [1]. Of the hearing loss disorders attributable to genetic causes, approximately 70% are classified as nonsyndromic since hearing impairment is the only symptom while 30% are classified as syndromic and are associated with other clinical features.…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients

Lee

Choi

Bae

et al. 2008

International Journal of Pediatric Otorhinolaryngology

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Objective-Mutations in the GJB2, GJB6 and SLC26A4 genes are a frequent cause of hearing loss in a number of populations. However, little is known about the genetic causes of hearing loss in the Korean population.Methods-We sequenced the GJB2 and GJB6 genes to examine the role of mutations in these genes in twenty-two hearing loss patients. We also sequenced the SLC26A4 gene in seven patients with inner ear malformations, including enlarged vestibular aqueduct (EVA) revealed by computer tomography.Results-Coding sequence mutations in GJB2 were identified in 13.6% of the patients screened. Two different mutations, 235delC and T86R were found in three unrelated patients. The 235delC was the most prevalent mutation with an allele frequency of 6.9% in our patient group. No mutations, including 342 kb deletion, were found in GJB6 gene. Three different variants of SLC26A4 were identified in the EVA patients, including one novel mutation. Four EVA patients carried two mutant alleles of SLC26A4, and at least one allele in all patients was the H723R mutation, which accounted for 75% of all mutant alleles.Conclusions-Our results suggest that GJB2 and SLC26A4 mutations together make up a major cause of congenital hearing loss in the Korean population. Further studies may be able to identify other common variants that account for a significant fraction of hearing loss in the Korean population.

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“…Permanent, congenital hearing loss affects approximately 1 in 500 infants and is an important cause of pediatric morbidity [Morton, 1991;Marazita et al, 1993]. Evidence that early diagnosis and subsequent intervention improves the outcome of these children has led to the development and implementation of statewide newborn hearing screening programs or early hearing loss detection and intervention (EHDI) programs…”

Section: Introductionmentioning

confidence: 99%

Methodology of a multistate study of congenital hearing loss: Preliminary data from Utah newborn screening

Dent

Kenneson

Palumbos

et al. 2004

American J of Med Genetics Pt C

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A multistate Centers for Disease Control and Prevention (CDC) study was designed to investigate the etiology of congenital hearing loss in infants ascertained through state-mandated hearing screening or early hearing loss detection and intervention (EHDI) programs. At least 50% of permanent childhood-onset hearing loss is due to genetic causes, and approximately 20% of all infants with congenital hearing loss have mutations in the GJB2 gene. Another 1% of childhood hearing loss is due to mitochondrial DNA (mtDNA) mutations. The specific aims of this study are to 1) classify the etiology of congenital hearing loss in infants by doing prospective genetic evaluations of all newborns with permanent hearing loss from defined geographic areas, 2) determine the frequency of mutations in GJB2 and two common mitochondrial mutations in these populations, and 3) establish a model infrastructure linking genetic services to statewide EHDI programs. As of April 2003, Utah is the only center evaluating patients. Study subjects identified through the Utah Department of Health EHDI program are contacted by letter and offered a comprehensive medical genetics evaluation with DNA testing for GJB2 and mitochondrial mutations A1555G and A7445G. To date, 25 probands and their immediate family members have been evaluated. We have identified 20 cases with nonsyndromic hearing loss (7 multiplex and 13 simplex), 4 with syndromic hearing loss, and 1 with presumed cytomegalovirus (CMV)-induced hearing loss. Six of 19 (32%) nonsyndromic cases with sensorineural hearing loss have mutations of one or both alleles of the GJB2 gene, and 21% are homozygous or compound heterozygotes for the 35delG mutation. No A1555G or A7445G mtDNA mutations have been found. Data reported to date include only children born in Utah, but EHDI programs in Hawaii, Rhode Island, and designated areas of Georgia have begun enrolling children in what is now a multistate collaborative study. This is the first comprehensive investigation to determine the etiology of hearing loss from populations ascertained through EHDI programs. The results of this study will facilitate the incorporation of genetic services into EHDI programs. ß

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Genetic epidemiological studies of early‐onset deafness in the U.S. school‐age population

Cited by 412 publications

References 2 publications

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss

Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients

Methodology of a multistate study of congenital hearing loss: Preliminary data from Utah newborn screening

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