Molecular screening of Japanese patients with gaucher disease: Phenotypic variability in the same genotypes

Kawame, Hiroshi; Maekawa, Kihei; Eto, Yoshikatsu

doi:10.1002/humu.1380020507

Cited by 16 publications

(8 citation statements)

References 22 publications

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“…In conclusion, our results emphasize the role of this relatively rare mutation in determining Gaucher disease; the presence in three different compound heterozygotes further explains the genotype/phenotype correlation (Theophilus et al 1989b, Zimran et al 1989, Kawame et al 1993, Sibille et al 1993, Sidransky et al 1994.…”

Section: Discussionsupporting

confidence: 73%

A rare G6490 → substitution at the last nucleotide of exon 10 of the glucocerebrosidase gene in two unrelated Italian Gaucher patients

et al. 1995

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Mutation screening of the glucocerebrosidase gene by SSCP analysis revealed an abnormal pattern of exon 10 in two unrelated Italian Gaucher patients. Direct sequencing of the mutated samples identified a G6490→ A transition. The same mutation has been described before in a Japanese patient with Gaucher disease type III. The clinical phenotype of our patients was type I in one whose second allele carried the N370S mutation and type II in the other one with a L444P mutation. In this latter the G6490→ A substitution cancels a normal Msp I site, while on the opposite chromosome the T6433→ C mutation (L444P) introduces a new Msp I site. Thus, digestion with Msp I of the amplified exon 10 is a useful method for identifying the two mutations simultaneously.

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Section: Discussionsupporting

confidence: 73%

A rare G6490 → substitution at the last nucleotide of exon 10 of the glucocerebrosidase gene in two unrelated Italian Gaucher patients

et al. 1995

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“…For example, one group has shown that mutations N370S, L444P, c.84-85insG, and IVS2ϩ1GrA account for 196% of the mutated alleles in Ashkenazi Jewish patients, although they constitute !75% of the mutated alleles in non-Jews (Beutler et al 1992;Beutler and Gelbart 1993). Among Japanese patients with Gaucher disease, neither mutation N370S nor c.84-85insG are seen, but L444P and F213I are relatively common, lending further support to the founder-effect theory (Kawame et al 1993;Eto and Ida 1999). In the Portuguese Gaucher population, the N370S mutation accounts for 63% of the mutated alleles, and two other rare mutations, G377S and N396T, are commonly encountered (Amaral et al 1993;Amaral et al 1999).…”

Section: Analysis and Classification Of 304 Mutant Alleles In Patientmentioning

confidence: 85%

Analysis and Classification of 304 Mutant Alleles in Patients with Type 1 and Type 3 Gaucher Disease

Koprivica

Stone

Park

et al. 2000

The American Journal of Human Genetics

286

246

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Gaucher disease results from the inherited deficiency of the enzyme glucocerebrosidase (EC 3.2.1.45). Although >100 mutations in the gene for human glucocerebrosidase have been described, most genotype-phenotype studies have focused upon screening for a few common mutations. In this study, we used several approaches-including direct sequencing, Southern blotting, long-template PCR, restriction digestions, and the amplification refraction mutation system (ARMS)-to genotype 128 patients with type 1 Gaucher disease (64 of Ashkenazi Jewish ancestry and 64 of non-Jewish extraction) and 24 patients with type 3 Gaucher disease. More than 97% of the mutant alleles were identified. Fourteen novel mutations (A90T, N117D, T134I, Y135X, R170C, W184R, A190T, Y304X, A341T, D399Y, c.153-154insTACAGC, c.203-204insC, c.222-224delTAC, and c.1122-1123insTG) and many rare mutations were detected. Recombinant alleles were found in 19% of the patients. Although 93% of the mutant alleles in our Ashkenazi Jewish type 1 patients were N370S, c.84-85insG, IVS2+1G-->A or L444P, these four mutations accounted for only 49% of mutant alleles in the non-Jewish type 1 patients. Genotype-phenotype correlations were attempted. Homozygosity or heterozygosity for N370S resulted in type 1 Gaucher disease, whereas homozygosity for L444P was associated with type 3. Genotype L444P/recombinant allele resulted in type 2 Gaucher disease, and homozygosity for a recombinant allele was associated with perinatal lethal disease. The phenotypic consequences of other mutations, particularly R463C, were more inconsistent. Our results demonstrate a high rate of mutation detection, a large number of novel and rare mutations, and an accurate assessment of the prevalence of recombinant alleles. Although some genotype-phenotype correlations do exist, other genetic and environmental factors must also contribute to the phenotypes encountered, and we caution against relying solely upon genotype for prognostic or therapeutic judgements.

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“…The procedures were based on the approach used for Gaucher's disease. 3,17 The primers used for the 754A mutation were 5'-GACTGGCAAGTGATAAGC-3' (sense) and 5'-GGTTACAGTGAGTGAAGA-3' (antisense). The PCR fragment was purified with the Geneclean II kit (Bio 101, La Jolla, California, U.S.A.).…”

Section: Methodsmentioning

confidence: 99%

Imprint Cytology of Gaucher’s Disease Presenting as a Splenic Mass

Kobayashi

Tamagaki²,

Yoneyama³

et al. 1998

Acta Cytologica

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Molecular screening of Japanese patients with gaucher disease: Phenotypic variability in the same genotypes

Cited by 16 publications

References 22 publications

A rare G6490 → substitution at the last nucleotide of exon 10 of the glucocerebrosidase gene in two unrelated Italian Gaucher patients

A rare G6490 → substitution at the last nucleotide of exon 10 of the glucocerebrosidase gene in two unrelated Italian Gaucher patients

Analysis and Classification of 304 Mutant Alleles in Patients with Type 1 and Type 3 Gaucher Disease

Imprint Cytology of Gaucher’s Disease Presenting as a Splenic Mass

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