Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features.
BACKGROUND: Wolfram syndrome (WFS) is a recessive neurologic and endocrinologic degenerative disorder, and is also known as DIDMOAD (Diabetes Insipidus, early-onset Diabetes Mellitus, progressive Optic Atrophy and Deafness) syndrome. Most affected individuals carry recessive mutations in the Wolfram...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4161373?pdf=render |
| _version_ | 1818528966406832128 |
|---|---|
| author | Kimie Matsunaga Katsuya Tanabe Hiroshi Inoue Shigeru Okuya Yasuharu Ohta Masaru Akiyama Akihiko Taguchi Yukari Kora Naoko Okayama Yuichiro Yamada Yasuhiko Wada Shin Amemiya Shigetaka Sugihara Yuzo Nakao Yoshitomo Oka Yukio Tanizawa |
| author_facet | Kimie Matsunaga Katsuya Tanabe Hiroshi Inoue Shigeru Okuya Yasuharu Ohta Masaru Akiyama Akihiko Taguchi Yukari Kora Naoko Okayama Yuichiro Yamada Yasuhiko Wada Shin Amemiya Shigetaka Sugihara Yuzo Nakao Yoshitomo Oka Yukio Tanizawa |
| author_sort | Kimie Matsunaga |
| collection | DOAJ |
| description | BACKGROUND: Wolfram syndrome (WFS) is a recessive neurologic and endocrinologic degenerative disorder, and is also known as DIDMOAD (Diabetes Insipidus, early-onset Diabetes Mellitus, progressive Optic Atrophy and Deafness) syndrome. Most affected individuals carry recessive mutations in the Wolfram syndrome 1 gene (WFS1). However, the phenotypic pleiomorphism, rarity and molecular complexity of this disease complicate our efforts to understand WFS. To address this limitation, we aimed to describe complications and to elucidate the contributions of WFS1 mutations to clinical manifestations in Japanese patients with WFS. METHODOLOGY: The minimal ascertainment criterion for diagnosing WFS was having both early onset diabetes mellitus and bilateral optic atrophy. Genetic analysis for WFS1 was performed by direct sequencing. PRINCIPAL FINDINGS: Sixty-seven patients were identified nationally for a prevalence of one per 710,000, with 33 patients (49%) having all 4 components of DIDMOAD. In 40 subjects who agreed to participate in this investigation from 30 unrelated families, the earliest manifestation was DM at a median age of 8.7 years, followed by OA at a median age of 15.8 years. However, either OA or DI was the first diagnosed feature in 6 subjects. In 10, features other than DM predated OA. Twenty-seven patients (67.5%) had a broad spectrum of recessive mutations in WFS1. Two patients had mutations in only one allele. Eleven patients (27.5%) had intact WFS1 alleles. Ages at onset of both DM and OA in patients with recessive WFS1 mutations were indistinguishable from those in patients without WFS1 mutations. In the patients with predicted complete loss-of-function mutations, ages at the onsets of both DM and OA were significantly earlier than those in patients with predicted partial-loss-of function mutations. CONCLUSION/SIGNIFICANCE: This study emphasizes the clinical and genetic heterogeneity in patients with WFS. Genotype-phenotype correlations may exist in patients with WFS1 mutations, as demonstrated by the disease onset. |
| first_indexed | 2024-12-11T06:56:57Z |
| format | Article |
| id | doaj.art-24509e5a11404243807f239b76ed7a91 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T06:56:57Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-24509e5a11404243807f239b76ed7a912022-12-22T01:16:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10690610.1371/journal.pone.0106906Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features.Kimie MatsunagaKatsuya TanabeHiroshi InoueShigeru OkuyaYasuharu OhtaMasaru AkiyamaAkihiko TaguchiYukari KoraNaoko OkayamaYuichiro YamadaYasuhiko WadaShin AmemiyaShigetaka SugiharaYuzo NakaoYoshitomo OkaYukio TanizawaBACKGROUND: Wolfram syndrome (WFS) is a recessive neurologic and endocrinologic degenerative disorder, and is also known as DIDMOAD (Diabetes Insipidus, early-onset Diabetes Mellitus, progressive Optic Atrophy and Deafness) syndrome. Most affected individuals carry recessive mutations in the Wolfram syndrome 1 gene (WFS1). However, the phenotypic pleiomorphism, rarity and molecular complexity of this disease complicate our efforts to understand WFS. To address this limitation, we aimed to describe complications and to elucidate the contributions of WFS1 mutations to clinical manifestations in Japanese patients with WFS. METHODOLOGY: The minimal ascertainment criterion for diagnosing WFS was having both early onset diabetes mellitus and bilateral optic atrophy. Genetic analysis for WFS1 was performed by direct sequencing. PRINCIPAL FINDINGS: Sixty-seven patients were identified nationally for a prevalence of one per 710,000, with 33 patients (49%) having all 4 components of DIDMOAD. In 40 subjects who agreed to participate in this investigation from 30 unrelated families, the earliest manifestation was DM at a median age of 8.7 years, followed by OA at a median age of 15.8 years. However, either OA or DI was the first diagnosed feature in 6 subjects. In 10, features other than DM predated OA. Twenty-seven patients (67.5%) had a broad spectrum of recessive mutations in WFS1. Two patients had mutations in only one allele. Eleven patients (27.5%) had intact WFS1 alleles. Ages at onset of both DM and OA in patients with recessive WFS1 mutations were indistinguishable from those in patients without WFS1 mutations. In the patients with predicted complete loss-of-function mutations, ages at the onsets of both DM and OA were significantly earlier than those in patients with predicted partial-loss-of function mutations. CONCLUSION/SIGNIFICANCE: This study emphasizes the clinical and genetic heterogeneity in patients with WFS. Genotype-phenotype correlations may exist in patients with WFS1 mutations, as demonstrated by the disease onset.http://europepmc.org/articles/PMC4161373?pdf=render |
| spellingShingle | Kimie Matsunaga Katsuya Tanabe Hiroshi Inoue Shigeru Okuya Yasuharu Ohta Masaru Akiyama Akihiko Taguchi Yukari Kora Naoko Okayama Yuichiro Yamada Yasuhiko Wada Shin Amemiya Shigetaka Sugihara Yuzo Nakao Yoshitomo Oka Yukio Tanizawa Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features. PLoS ONE |
| title | Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features. |
| title_full | Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features. |
| title_fullStr | Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features. |
| title_full_unstemmed | Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features. |
| title_short | Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features. |
| title_sort | wolfram syndrome in the japanese population molecular analysis of wfs1 gene and characterization of clinical features |
| url | http://europepmc.org/articles/PMC4161373?pdf=render |
| work_keys_str_mv | AT kimiematsunaga wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT katsuyatanabe wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT hiroshiinoue wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT shigeruokuya wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT yasuharuohta wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT masaruakiyama wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT akihikotaguchi wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT yukarikora wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT naokookayama wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT yuichiroyamada wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT yasuhikowada wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT shinamemiya wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT shigetakasugihara wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT yuzonakao wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT yoshitomooka wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures AT yukiotanizawa wolframsyndromeinthejapanesepopulationmolecularanalysisofwfs1geneandcharacterizationofclinicalfeatures |