Mutations in the Wolfram Syndrome Type 1 Gene (WFS1) Define a Clinical Entity of Dominant Low-Frequency Sensorineural Hearing Loss

Lesperance, Marci M.; Hall, James W.; Agustin, Theresa B. San; Leal, Suzanne M.

doi:10.1001/archotol.129.4.411

Cited by 59 publications

(35 citation statements)

References 35 publications

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“…In DNFA6/14/ 38 there is no or only mild progression of hearing loss. Some patients have also reported tinnitus, but none reported vertigo or dizziness (Young et al 2001;Lesperance et al 2003;Pennings et al 2003). In the present study, two out of nine patients noticed tinnitus, but none had progression of hearing loss or vertigo, in line with the previously reported phenotype.…”

Section: Discussionsupporting

confidence: 91%

Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese

Fukuoka¹,

Kanda²,

Ohta

et al. 2007

J Hum Genet

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Mutations in WFS1 are reported to be responsible for two conditions with distinct phenotypes; DFNA6/ 14/38 and autosomal recessive Wolfram syndrome. They differ in their associated symptoms and inheritance mode, and although their most common clinical symptom is hearing loss, it is of different types. While DNFA6/14/38 is characterized by low frequency sensorineural hearing loss (LFSNHL), in contrast, Wolfram syndrome is associated with various hearing severities ranging from normal to profound hearing loss that is dissimilar to LFSNHL (Pennings et al. 2002). To confirm whether within non-syndromic hearing loss patients WFS1 mutations are found restrictively in patients with LFSNHL and to summarize the mutation spectrum of WFS1 found in Japanese, we screened 206 Japanese autosomal dominant and 64 autosomal recessive (sporadic) non-syndromic hearing loss probands with various severities of hearing loss. We found three independent autosomal dominant families associated with two different WFS1 mutations, A716T and E864K, previously detected in families with European ancestry. Identification of the same mutations in independent families with different racial backgrounds suggests that both sites are likely to be mutational hot spots. All three families with WFS1 mutations in this study showed a similar phenotype, LFSNHL, as in previous reports. In this study, onethird (three out of nine) autosomal dominant LFSNHL families had mutations in the WFS1 gene, indicating that in non-syndromic hearing loss WFS1 is restrictively and commonly found within autosomal dominant LFSNHL families.

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Section: Discussionsupporting

confidence: 91%

Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese

Fukuoka¹,

Kanda²,

Ohta

et al. 2007

J Hum Genet

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“…In some patients, however, audiometric thresholds at higher frequencies deteriorate with increasing age, resulting in horizontal HL in middle age and high-frequency HL above the age of 60 years [8,22]. Some patients have also reported tinnitus, but none reported vertigo or dizziness [8,23,24]. In this study, the affected family members carrying the A844T mutation showed no subjective progression of hearing impairment or vestibular symptoms, which is consistent with the symptoms of DFNA6/14.…”

Section: Discussionsupporting

confidence: 84%

A mutation in Wolfram syndrome type 1 gene in a Japanese family with autosomal dominant low-frequency sensorineural hearing loss

Noguchi¹,

Yashima²,

Hatanaka³

et al. 2005

Acta Oto-Laryngologica

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One patient carried a heterozygous G2700A mutation at codon 844 in exon 8, resulting in substitution of a threonine for an alanine (A844T). Genetic analysis of the available members of the patient's family showed that the A844T mutation segregated with LFSNHL, but was not detected in any of 140 control chromosomes. It thus appears likely that the A844T mutation is causative for hearing loss in this group. Speech audiometry, self-recording audiometry and auditory brainstem responses showed the patient to have cochlear deafness without retrocochlear dysfunction. No mutation was found in the other two patients.

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“…Hearing impairment (HI) in Wolfram syndrome is progressive and mainly affects the high frequencies [Cremers et al, 1977;Higashi, 1991], with affected females showing significantly more HI than affected males [Pennings et al, in press]. In contrast, HI associated with DFNA6/14 only affects the low frequencies and it shows little or no progression [The Vanderbilt University Hereditary Deafness Study Group, 1968;Kunst et al, 1999;Brodwolf et al, 2001;Bom et al, 2002;Huygen et al, 2002;Lesperance et al, 2003;Pennings et al, 2003]. DFNA1 (MIM# 124900) is currently the only other known deafness locus that affects the low frequencies [Lynch et al, 1997].…”

Section: Introductionmentioning

confidence: 99%

Mutational spectrum of theWFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease

Cryns

Sivakumaran

Ouweland³

et al. 2003

Hum. Mutat.

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WFS1 is a novel gene and encodes an 890 amino-acid glycoprotein (wolframin), predominantly localized in the endoplasmic reticulum. Mutations in WFS1 underlie autosomal recessive Wolfram syndrome and autosomal dominant low frequency sensorineural hearing impairment (LFSNHI) DFNA6/14. In addition, several WFS1 sequence variants have been shown to be significantly associated with diabetes mellitus and this gene has also been implicated in psychiatric diseases. Wolfram syndrome is highly variable in its clinical manifestations, which include diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. Wolfram syndrome mutations are spread over the entire coding region, and are typically inactivating, suggesting that a loss of function causes the disease phenotype. In contrast, only non-inactivating mutations have been found in DFNA6/14 families, and these mutations are mainly located in the C-terminal protein domain. In this paper, we provide an overview of the currently known disease-causing and benign allele variants of WFS1 and propose a potential genotype-phenotype correlation for Wolfram syndrome and LFSNHI.

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Mutations in the Wolfram Syndrome Type 1 Gene (WFS1) Define a Clinical Entity of Dominant Low-Frequency Sensorineural Hearing Loss

Cited by 59 publications

References 35 publications

Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese

Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese

A mutation in Wolfram syndrome type 1 gene in a Japanese family with autosomal dominant low-frequency sensorineural hearing loss

Mutational spectrum of theWFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease

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