Sex-Related Hearing Impairment in Wolfram Syndrome Patients Identified by Inactivating &lt;i&gt;WFS1&lt;/i&gt; Mutations

Pennings, Ronald J.E.; Huygen, P.L.M.; Ouweland, Jody M.W. van den; Cryns, Kim; Dikkeschei, L. D.; Camp, Guy Van; Cremers, C.W.R.J.

doi:10.1159/000074187

Cited by 26 publications

(34 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This mutation was not associated with low-frequency hearing impairment in the heterozygous carriers. 18,29 ClustalW analysis 30 of WFS1 revealed this aspartic acid residue is conserved in different mammals (Figure 2). The c.1456C 4T (p.Gln486*) was identified in a mother and daughter from a non-consanguineous Italian family.…”

Section: Discussionmentioning

confidence: 99%

Identification of homozygous WFS1 mutations (p.Asp211Asn, p.Gln486*) causing severe Wolfram syndrome and first report of male fertility

Haghighi

Setoodeh

et al. 2012

Eur J Hum Genet

View full text Add to dashboard Cite

Wolfram syndrome (WFS) is a neurodegenerative genetic condition characterized by juvenile-onset of diabetes mellitus and optic atrophy. We studied clinical features and the molecular basis of severe WFS (neurodegenerative complications) in two consanguineous families from Iran. A clinical and molecular genetic investigation was performed in the affected and healthy members of two families. The clinical diagnosis of WFS was confirmed by the existence of diabetes mellitus and optic atrophy in the affected patients, who in addition had severe neurodegenerative complications. Sequencing of WFS1 was undertaken in one affected member from each family. Targeted mutations were tested in all members of relevant families. Patients had most of the reported features of WFS. Two affected males in the first family had fathered unaffected children. We identified two homozygous mutations previously reported with apparently milder phenotypes: family 1: c.631G4A (p.Asp211Asn) in exon 5, and family 2: c.1456C4T (p.Gln486*) in exon 8. Heterozygous carriers were unaffected. This is the first report of male Wolfram patients who have successfully fathered children. Surprisingly, they also had almost all the complications associated with WFS. Our report has implications for genetic counseling and family planning advice for other affected families.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of homozygous WFS1 mutations (p.Asp211Asn, p.Gln486*) causing severe Wolfram syndrome and first report of male fertility

Haghighi

Setoodeh

et al. 2012

Eur J Hum Genet

View full text Add to dashboard Cite

show abstract

“…LFSNHL DFNA6/14/38 is a rare, but clearly differentiated type of hearing loss affecting the low frequencies (2,000 Hz and below) that worsens over time, but does not progress to profound deafness. Wolfram syndrome is characterized by diabetes mellitus, diabetes insipidus, optic atrophy (Strom et al 1998;Inoue et al 1998) and normal or high/all frequency hearing loss with various hearing severities ranging from mild to profound (Pennings et al 2004). Since WFS1 mutations have been found in various types of hearing loss, it was an interesting question whether WFS1 mutations could be found in nonsyndromic hearing loss patients with other than LFSNHL, but there had been no reports of mutation screening for various phenotypes of hearing.…”

Section: Introductionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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.

show abstract

“…As it is well known, WFS1 gene is associated with not only Wolfram syndrome but LFSNHL as well. Audiograms of Wolfram syndrome patients showed hearing impairment involving the middle and high frequencies [Pennings et al, 2004]. Whereas, all of 28 WFS1 mutations, which have been reported to lead to non-syndromic sensorineural hearing loss (Table VI) causing hearing loss in low frequency.…”

Section: Discussionmentioning

confidence: 97%

“…Also, many patients develop urinarytract atony, ataxia, peripheral neuropathy, and psychiatric illness. Audiograms of patients diagnosed with Wolfram syndrome typically show hearing impairment involving the middle and high frequencies [Pennings et al, 2004]. In contrast, heterozygous mutations in WFS1 gene cause the autosomal dominantly nonsyndromic low frequency hearing impairment [Tsai et al, 2007].…”

Section: Introductionmentioning

confidence: 99%

Identification of a novel missense mutation in the WFS1 gene as a cause of autosomal dominant nonsyndromic sensorineural hearing loss in all‐frequencies

Bai

Zhang

et al. 2014

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Hearing loss is the most common sensory disorder affecting 278 million people in the world, and more than 60% of hearing loss patients can be attributed to genetic causes. Although many loci have been linked to hereditary hearing impairment, most of the causative genes have not been identified as yet. The goal of this study was to investigate the cause of dominantly inherited sensorineural all-frequency hearing loss in a six-generation Chinese family. We performed exome sequencing to screen responsible candidate genes in three family members with all-frequency hearing loss and one member with normal hearing. Sanger sequencing was employed to examine the variant mutations in the members of this family and 200 healthy persons. PCR-RFLP was performed to further confirm the nucleotide mutation. A novel missense mutation c.2389G > A (GAC → AAC) in WFS1 gene was identified, which was co-segregated with the hearing loss phenotype. No mutation was found in 200 controls and the family members with normal hearing in this site. The present study identifies, for the first time, a novel mutation in WFS1 gene that causes non-syndromic hearing loss in all, rather than in low or high, frequencies.

show abstract

Sex-Related Hearing Impairment in Wolfram Syndrome Patients Identified by Inactivating <i>WFS1</i> Mutations

Cited by 26 publications

References 25 publications

Identification of homozygous WFS1 mutations (p.Asp211Asn, p.Gln486*) causing severe Wolfram syndrome and first report of male fertility

Identification of homozygous WFS1 mutations (p.Asp211Asn, p.Gln486*) causing severe Wolfram syndrome and first report of male fertility

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

Identification of a novel missense mutation in the WFS1 gene as a cause of autosomal dominant nonsyndromic sensorineural hearing loss in all‐frequencies

Contact Info

Product

Resources

About