Gaucher disease (Norrbottnian type III): probable founders identified by genealogical and molecular studies

Dahl, Niklas; Hillborg, Per-Olof; Olofsson, Agneta

doi:10.1007/bf00216461

Cited by 18 publications

(9 citation statements)

References 6 publications

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“…Together with the occurrence of L444P in Europeans, Mexicans, Africans, Arabs and Filipinos (Beutler and Gelbart 1993) as well as Japanese, our data provide further evidence of the heterogeneous origin of L444P, although its spread by a founder effect has been documented in Sweden (Dahl et al 1993). After L444P/L444P, the L444P/ F213I GD genotype is the second most common among Japanese patients, as the F213I (754A) mutation is the second most common GD mutation in Japan, accounting for 15% of total GD alleles (Ida et al 1997).…”

Section: Discussionmentioning

confidence: 56%

Clinical and genetic studies of Japanese homozygotes for the Gaucher disease L444P mutation

Ida

Rennert²,

Iwasawa

et al. 1999

Hum Genet

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In patients originally genotyped as homoallelic for the Gaucher disease (GD) L444P (1448C) mutation, we sought to confirm previously reported phenotypic differences between Caucasians and Japanese, to determine the prevalence and phenotypic impact of recombinant alleles, and to explore the phenotypic influence of genetic background. We therefore analyzed data from longer-term clinical follow-up, more comprehensive genotyping and polymorphism and mitochondrial DNA (mtDNA) testing in all known Japanese L444P homozygotes (n=15). Our studies demonstrated that, of 12 patients in our series originally diagnosed with non-neuronopathic GD, 9 developed neurological signs/symptoms during follow-up (at a mean of 14 years 11 months +/- 11 years 4 months). Of three patients originally diagnosed with acute neuronopathic (type 2) GD, all three were compound heterozygotes for L444P and the complex allele RecNci I. In the entire series, Pvu II and liver erythrocyte pyruvate kinase (PKLR) polymorphism and prevalence of the 9 bp mtDNA deletion were heterogeneous, and these background genetic factors could not predict phenotypic expression. Our data suggest that, in Japanese as in Caucasian patients, the L444P/L444P genotype is highly associated with subacute neuronopathic (type 3) GD, and the presence of a complex allele together with an L444P allele leads to type 2 disease. Our findings also underline the importance of comprehensive genotyping (particularly testing for recombinant alleles), long-term follow-up and careful neurological examination in patients with early-onset GD. Such measures ultimately may improve genotype/phenotype correlations and, with them, genetic counseling and therapeutic decision making.

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Section: Discussionmentioning

confidence: 56%

Clinical and genetic studies of Japanese homozygotes for the Gaucher disease L444P mutation

Ida

Rennert²,

Iwasawa

et al. 1999

Hum Genet

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“…Interestingly, a few recurrent GBA mutations, including p.N409S in Ashkenazi Jewish and European communities [11], p.D448H in northern Swedish [12], p.W417G in French-Canadian [13], and p.G416S in Tabuleiro do Norte, Northeastern Brazilian [14] populations have been suggested as founder mutations.…”

Section: Introductionmentioning

confidence: 99%

The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

Kim

Choi

Kim

et al. 2020

Preprint

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Background Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients. Results The study cohort included 63 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harboured the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (10%). Of the 18 patients harbouring the p.G85E mutation, their median age at diagnosis was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3,075 years. Conclusion The GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.

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“…Its presence in either the heterozygous or homozygous state is protective against the development of neurologic involvement. Another common mutation, L444P, is also pan‐ethnic, common within the population of Northern Sweden [Iselius et al, 1989; Dahl et al, 1993], and when present in the homozygous state has a clinical presentation in early childhood that is often associated with neurologic symptoms.…”

Section: Introductionmentioning

confidence: 99%

Novel mutation, L371V, causing multigenerational Gaucher disease in a Lebanese family

Shamseddine

Taher

Fakhani

et al. 2003

American J of Med Genetics Pt A

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We have identified six individuals over three generations within a Lebanese-Arab family affected with Gaucher disease. This family is unusual and informative because affected members are homozygous for a previously unidentified mutation, L371V. Clinical symptoms begin in early childhood and progress to moderately severe involvement by young adulthood. There is significant anemia, thrombocytopenia, and bony involvement, but no mental deterioration. The phenotype is more severe than the phenotype observed in the common mutation associated with type 1 Gaucher disease, N370S. It is unknown whether L371V is a private mutation limited to this family, or will prove to be a common mutation within the Lebanese population.

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Gaucher disease (Norrbottnian type III): probable founders identified by genealogical and molecular studies

Cited by 18 publications

References 6 publications

Clinical and genetic studies of Japanese homozygotes for the Gaucher disease L444P mutation

Clinical and genetic studies of Japanese homozygotes for the Gaucher disease L444P mutation

The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

Novel mutation, L371V, causing multigenerational Gaucher disease in a Lebanese family

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