Prevalent and rare mutations among Gaucher patients

Eyal, Nurit; Wilder, Sylvia; Horowitz, Mia

doi:10.1016/0378-1119(90)90264-r

Cited by 114 publications

(60 citation statements)

References 22 publications

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“…A prevalent class of mutant alleles encountered in patients with GD is due to recombination events [Eyal et al, 1990;Hong et al, 1990;Latham et al, 1990Latham et al, , 1991Tayebi et al, 2003;Zimran et al, 1990b]. Such alleles have been designated as ''complex'' alleles [Latham et al, 1990], ''pseudopattern'' or ''psi'' [Hong et al, 1990], ''rec''' for ''recombinant'' [Eyal et al, 1990], ''fusion'' alleles [Zimran et al, 1990b], and ''chimeric'' alleles [Sarria et al, 1999]).…”

Section: Recombinant and Complex Allelesmentioning

confidence: 99%

“…Such alleles have been designated as ''complex'' alleles [Latham et al, 1990], ''pseudopattern'' or ''psi'' [Hong et al, 1990], ''rec''' for ''recombinant'' [Eyal et al, 1990], ''fusion'' alleles [Zimran et al, 1990b], and ''chimeric'' alleles [Sarria et al, 1999]). Recombination within the glucocerebrosidase locus appears to be enhanced by the high degree of sequence identity and the close physical proximity of the GBA pseudogene.…”

Section: Recombinant and Complex Allelesmentioning

confidence: 99%

“…A useful distinction for molecular diagnostic applications is that the pseudogene carries a 55-bp deletion in exon 9. As will be discussed further, the presence of this conserved pseudogene at the same locus is significant, because recombination events between GBAP and GBA result in several different Gaucher mutations and groups of mutations [Eyal et al, 1990;Hong et al, 1990;Latham et al, 1990Latham et al, , 1991Zimran, et al, 1990b].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Recombinant and Complex Allelesmentioning

confidence: 99%

Section: Recombinant and Complex Allelesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

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“…Compared with other methods including conventional PCR-directed sequencing of GBA gDNA or cDNA, 8,9 restriction enzyme digestion of PCR amplification products, 10 and Southern blot analysis, 4,11 the most valuable advantage of our approach is that it is very easy to determine the presence of gene fusion or duplication alleles by simply interpreting PCR result as either 'on' or 'off ' , although sequencing of PCR amplicons is required to determine the precise converted regions, like in other methods. 4,8,9,11 As there is no sequence difference in the intron 10 exon 11 regions between GBA and GBAP ( Supplementary Figure 1), when the reverse primers corresponding to the end of GBA gene alone are used as in the conventional PCR-based methods, 9 it is difficult to distinguish gene conversion alleles from reciprocal gene fusion alleles, which leads to genotyping error.…”

Section: Resultsmentioning

confidence: 99%

“…4,8,9,11 As there is no sequence difference in the intron 10 exon 11 regions between GBA and GBAP ( Supplementary Figure 1), when the reverse primers corresponding to the end of GBA gene alone are used as in the conventional PCR-based methods, 9 it is difficult to distinguish gene conversion alleles from reciprocal gene fusion alleles, which leads to genotyping error. We solved this problem by using the reverse primer (cMTX1-r) corresponding to the contiguous MTX1P gene (Figure 1a).…”

Section: Resultsmentioning

confidence: 99%

Identification of a novel recombinant mutation in Korean patients with Gaucher disease using a long-range PCR approach

et al. 2011

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Gaucher disease (GD) is an autosomal recessive, lysosomal disorder caused by mutations in the gene for the b-glucocerebrosidase (GBA) enzyme. Presence of the non-functional GBAP pseudogene, which shares high sequence similarity with the functional GBA gene, has made it difficult to carry out molecular analyses of GD, especially recombinant mutations. Using a long-range PCR approach that has been skillfully devised for the easy detection of GBA recombinant mutations, we identified four recombinant mutations including two gene conversion alleles, Rec 1a and Rec 8a, one reciprocal gene fusion allele, Rec 1b, and one reciprocal gene duplication allele, Rec 7b, in Korean patients with GD. Rec 8a, in which the GBAP pseudogene sequence from intron 5 to exon 11 is substituted for the GBA gene is a novel recombinant mutation. All mutations were confirmed by full sequencing of PCR amplicons and/or Southern blot analysis. These results indicate that the usage of long-range PCR may allow the rapid and accurate detection of GBA recombinant mutations and contribute to the improvement of genotyping efficiency in GD patients.

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