Genetic Diagnosis of Werner's Syndrome, a Premature Aging Disease, by Mutant Allele Specific Amplification (MASA) and Oligomer Ligation Assay (OLA)

Matsumoto, Takehisa; Tsuchihashi, Zenta; Ito, Chie; Fujita, Kumiko; Goto, Makoto; Furuichi, Yasuhiro

doi:10.1089/rej.1.1998.1.131

Cited by 15 publications

(10 citation statements)

References 4 publications

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“…Consistent with our previous reports [17,18], type 4 and type 6 mutations on the Werner helicase gene were found to be the two major mutations; these mutations comprised 50.0 and 31.8%, respectively, of the total in a sample of 44 chromosomes. The lack of correlation of serum and urine HA levels with the mutation types of the Werner helicase gene clearly indicates that the determination of serum and urine HA levels contributes to the diagnosis of WS irrespective of the mutation type.…”

Section: Discussionsupporting

confidence: 91%

“…The specific mutations for WS were found in the patients examined [17,18]. Care was taken to exclude individuals with inflammatory diseases, and abnormal liver and renal function.…”

Section: Patients and Specimensmentioning

confidence: 99%

“…Mutation on the WS helicase gene was analyzed by mutantallele-specific amplification and oligomer ligation assay [18]. Mutation of positive DNAs was confirmed by the sequence of the PCR products around the mutation site.…”

Section: Determination Of Mutation On the Ws Helicase Genementioning

confidence: 99%

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Elevation of Serum Hyaluronan Level in Werner’s Syndrome

Tanabe¹,

Goto²

2001

Gerontology

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Background: There is a well-established association between Werner’s syndrome (WS) and hyperhyaluronic aciduria; however, to date hyaluronan (HA) in the serum has not been statistically linked with WS. Recently, the gene that causes WS has been defined as a DNA helicase on chromosome 8, and 19 different mutations in WS patients have been identified. It is not known whether the mutation type of the Werner helicase gene affects the levels of serum and urine HA in WS patients. Objective: To evaluate the association of serum HA with WS, and the relationship of the serum and urine HA levels to the mutation type. Methods: HA both in the serum and the urine was measured in 40 patients with WS and 114 normal controls. The serum and urine HA were quantified by sandwich binding protein assay and competitive ELISA-like method, respectively. The muation on WS helicase gene was analyzed by mutant-allele-specific amplification and oligomer ligation assay. Results: WS patients showed significantly higher levels of HA in the serum (mean ± SD: 115.7 ± 119.8 ng/ml, p < 0.001) and urine (1,040.8 ± 777.3 ng/mg creatinine, Cre, p < 0.001) than age-matched controls (serum HA: 15.8 ± 14.2 ng/ml, urine HA: 379.7 ± 124.2 ng/mg Cre). The serum and urine HA levels of WS patients are almost equal to those of normal controls over 80 years (serum HA: 118.5 ± 108.4 ng/ml, urine HA: 914.5 ± 712.1 ng/mg Cre). There was a significant correlation between serum and urine HA levels in WS patients (r = 0.42, p = 0.007). Analysis of the mutation on the helicase gene in 22 WS patients showed that among 44 chromosomes, 3 (6.8%) chromosomes had type 1 mutation, 22 (50.0%) had type 4 mutation, 14 (31.8%) had type 6 mutation, and the rest had other mutations. The serum and urine levels of HA did not show any significant association with the mutation type. Conclusion: The hyperhyaluronic aciduria in WS reflects the high level of serum HA. The serum and urine HA levels are useful biochemical markers for WS irrespective of the muation type of the Werner helicase gene.

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Section: Discussionsupporting

confidence: 91%

“…The specific mutations for WS were found in the patients examined [17,18]. Care was taken to exclude individuals with inflammatory diseases, and abnormal liver and renal function.…”

Section: Patients and Specimensmentioning

confidence: 99%

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Elevation of Serum Hyaluronan Level in Werner’s Syndrome

Tanabe¹,

Goto²

2001

Gerontology

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“…Approximately 200 Japanese WS patients (WS0101-WS60001) diagnosed by our criteria were further confirmed by the loss of intact WRN protein and the presence of WRN mutations as previously reported (3,16,17). B-lymphoblastoid cells and skin fibroblasts from ~200 WS patients and their family members are deposited at RIKEN Bio-Resource Center (Tsukuba Japan) as Goto Collection of Werner Syndrome and can be used by researchers upon request (http://biolod.org/ class/cria304u12i/Goto_Collection_EBV_transformed_ B_cell_lines_ and_primary_fibroblast_derived_from_ Werner_syndrome_patient).…”

Section: Databasesupporting

confidence: 79%

“…html), the number of the mutation type has accumulated up to ~100 worldwide. Approximately 200 Japanese WS patients (WS0101-WS61901) diagnosed by our criteria were further confirmed by the loss of intact WRN protein and the presence of WRN mutations (3,16,17). Although the precise mutation in ~15% patients with defective WRN protein is not identified yet, the mutation types so-far recognized in Japan are quite different from those outside Japan as shown in Table 3.…”

Section: Geographical Distribution and Mutation Typementioning

confidence: 63%