Mutation analysis in 46 British and Irish patients with Gaucher's disease

Hatton, C. E.; Cooper, Alan; Whitehouse, C.; Wraith, J. Edmond

doi:10.1136/adc.77.1.17

Cited by 48 publications

(27 citation statements)

References 16 publications

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“…The percentage of unknown alleles (11.5%) corresponds with the results of other studies of European populations (Cormand et al, 1995;Tylki-Szymanska et al, 1996;Boot et al, 1997;Grabowski, 1997;Hatton et al, 1997;le Coutre et al, 1997) except for those performed on a limited number of patients or carried out by complete gene sequencing (Germain et al, 1998). Since we often receive the DNAs from other referring centres, the amount or quantity of the sample does not always allow us to sequence the whole gene.…”

Section: Discussionsupporting

confidence: 80%

Analysis of the glucocerebrosidase gene and mutation profile in 144 Italian gaucher patients

et al. 2002

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Gaucher disease (GD), the most prevalent lysosomal storage disease characterized by a remarkable degree of clinical variability, results from deleterious mutations in the glucocerebrosidase gene (GBA). In this paper we report the molecular characterization of 144 unrelated Italian GD patients with the three types of the disease. The allelic frequencies of Italians are reported and the mutation profile is analyzed. Besides the common N370S, L444P, RecNciI, G202R, IVS2+1G>A, D409H, F213I mutations, the different molecular strategies, used for the mutation detection, identified the rare N107L, R131C, R170C, R170P, N188S, S196P, R285C, R285H, W312C, D399N, A446P, IVS10-1G>A, Rec∆55, total gene deletion, as well as 12 mutant alleles that were exclusively present in the Italian population until now: the previously reported R353G, N370S+S488P mosaicism, IVS8(-11delC)-14T>A), Rec I, Y418C, and the seven novel alleles D127X, P159T, V214X, T231R, L354X, H451R, and G202R+M361I. The wide phenotypic differences observed within the genotypic groups as well as between siblings implicate a significant contribution of other modifying genetic and/or non-genetic factors and claim a comprehensive valuation of the patient including clinical., biochemical and molecular investigations for prognosis, appropriate interventive therapy and reliable genetic counseling.

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Section: Discussionsupporting

confidence: 80%

Analysis of the glucocerebrosidase gene and mutation profile in 144 Italian gaucher patients

et al. 2002

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“…Likewise, individuals homozygous for c.754T4A (F213I) or c.1448T4C (L444P) usually develop chronic neuronopathic GD [Ida et al, 1996;Koprivica et al, 2000], but either mutation together with a null allele is more likely to have a type 2 phenotype [Stone et al, 2000b]. Mutation c.1504C4T (R463C) is particularly confusing, as homozygotes have been described with type 1 disease [Hatton et al, 1997], yet when inherited with a null allele, either type 1 or type 3 ensues [Koprivica et al, 2000].…”

Section: Clinical Significancementioning

confidence: 99%

Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA)

et al. 2008

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Communicated by William S. SlyGaucher disease (GD) is an autosomal recessive disorder caused by the deficiency of glucocerebrosidase, a lysosomal enzyme that catalyses the hydrolysis of the glycolipid glucocerebroside to ceramide and glucose. Lysosomal storage of the substrate in cells of the reticuloendothelial system leads to multisystemic manifestations, including involvement of the liver, spleen, bone marrow, lungs, and nervous system. Patients with GD have highly variable presentations and symptoms that, in many cases, do not correlate well with specific genotypes. Almost 300 unique mutations have been reported in the glucocerebrosidase gene (GBA), with a distribution that spans the gene. These include 203 missense mutations, 18 nonsense mutations, 36 small insertions or deletions that lead to either frameshifts or in-frame alterations, 14 splice junction mutations, and 13 complex alleles carrying two or more mutations in cis. Recombination events with a highly homologous pseudogene downstream of the GBA locus also have been identified, resulting from gene conversion, fusion, or duplication. In this review we discuss the spectrum of GBA mutations and their distribution in the patient population, evolutionary conservation, clinical presentations, and how they may affect the structure and function of glucocerebrosidase.

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“…The entire coding region of the glucocerebrosidase gene was amplified by PCR using primers and conditions shown in Table 1 or previously described. 9 Each exon was sequenced using an ABI prism 377 sequencer and the dRhodamine sequencing kit (Applied Biosystems, Warrington, UK) according to the manufacturer's instructions as previously described. 9 …”

Section: Methodsmentioning

confidence: 99%

“…9 Each exon was sequenced using an ABI prism 377 sequencer and the dRhodamine sequencing kit (Applied Biosystems, Warrington, UK) according to the manufacturer's instructions as previously described. 9 …”

Section: Methodsmentioning

confidence: 99%

Homozygous loss of a cysteine residue in the glucocerebrosidase gene results in Gaucher's disease with a hydropic phenotype

et al. 2004

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Mutation analysis in 46 British and Irish patients with Gaucher's disease

Abstract: DNA from 46 unrelated patients with

Cited by 48 publications

References 16 publications

Analysis of the glucocerebrosidase gene and mutation profile in 144 Italian gaucher patients

Analysis of the glucocerebrosidase gene and mutation profile in 144 Italian gaucher patients

Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA)

Homozygous loss of a cysteine residue in the glucocerebrosidase gene results in Gaucher's disease with a hydropic phenotype

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