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. 2021 Nov 11:29:100820.
doi: 10.1016/j.ymgmr.2021.100820. eCollection 2021 Dec.

Long-read single molecule real-time (SMRT) sequencing of GBA1 locus in Gaucher disease national cohort from Argentina reveals high frequency of complex allele underlying severe skeletal phenotypes: Collaborative study from the Argentine Group for Diagnosis and Treatment of Gaucher Disease

Guillermo I Drelichman  1 , Nicolas Fernández Escobar  1 , Barbara C Soberon  1 , Nora F Basack  1 , Joaquin Frabasil  2 , Andrea B Schenone  2 , Gabriel Aguilar  3 , Maria S Larroudé  3 , James R Knight  4 , Dejian Zhao  4 , Jiapeng Ruan  5 , Pramod K Mistry  5 ; Argentine Group for Diagnosis and Treatment of Gaucher Disease
Affiliations

Long-read single molecule real-time (SMRT) sequencing of GBA1 locus in Gaucher disease national cohort from Argentina reveals high frequency of complex allele underlying severe skeletal phenotypes: Collaborative study from the Argentine Group for Diagnosis and Treatment of Gaucher Disease

Guillermo I Drelichman et al. Mol Genet Metab Rep. .

Abstract

Gaucher disease is reckoned for extreme phenotypic diversity that does not show consistent genotype/phenotype correlations. In Argentina, a national collaborative group, Grupo Argentino de Diagnóstico y Tratamiento de la Enfermedad de Gaucher, GADTEG, have delineated uniformly severe type 1 Gaucher disease manifestations presenting in childhood with large burden of irreversible skeletal disease. Here using Long-Read Single Molecule Real-Time (SMRT) Sequencing of GBA1 locus, we show that RecNciI allele is highly prevalent and associates with severe skeletal manifestations in childhood.

Keywords: BD, bone disease; Bone disease; ERT, Enzyme replacement therapy; GADTEG, The Argentine Group for Diagnosis and Treatment of Gaucher Disease (Grupo Argentino de Diagnóstico y Tratamiento de la Enfermedad de Gaucher; GD, Gaucher disease; GL1, Glucosylceramide; Gaucher disease; Genotype phenotype correlation; Mutation analysis.

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Figures

Fig. 1
Fig. 1
Location of GBA1 on Chromosome 1q21 with flanking genes, and the LR-PCR amplicons for SMRT sequencing. The 133kb human GBA1 loci (GRCh38.p13, Chr1q22; NC_000001.11) consist of 15 genes: PKLR (pyruvate kinase L/R, Chr1:155,289,293..155,301,438. Length:12,146nt); HCN3 (hyperpolarization activated cyclic nucleotide gated potassium channel 3, complement Chr1:155,277,427..155,289,848. Length:12,422nt), CLK2 (CDC like kinase 2, Chr1:155,262,868..155,273,504. Length:10,637nt), SCAMP3 (secretory carrier membrane protein 3, Chr1:155,255,981..155,262,360. Length:6,380nt), FAM189B (family with sequence similarity 189 member B, Chr1:155,247,205..155,255,892. Length:8,688nt), GBA1 (glucosylceramidase beta, Chr1:155,234,452..155,244,627. Length:10,176nt), MTX1P1 (metaxin 1 pseudogene 1, complement Chr1:155,230,976..155,234,451. Length:3,476nt), GBAP1 (glucosylceramidase beta pseudogene 1, Chr1:155,213,825..155,227,534. Length:13,710nt), MTX1 (metaxin 1, complement Chr1:155,208,699..155,213,839. Length:5,141nt), THBS3 (thrombospondin 3, Chr1:155,195,588..155,209,180. Length:13,593nt), LOC (THBS3-AS1/LOC105371450, complement Chr 155,196,035..155,200,571. Length:4,537nt), MIR92B (microRNA 92b, complement Chr1:155,195,177..155,195,272. Length:96nt), TRIM46 (tripartite motif containing 46, complement Chr1:155,173,381..155,184,971. Length:11,591nt), MUC1 (mucin 1, cell surface associated, Chr1:155,185,824..155,192,915. Length:7,092nt), KRTCAP2 (keratinocyte associated protein 2, Chr1:155,169,408..155,173,304. Length:3,897nt). GBA1 pseudogene (GBAP1) is approximately 12 kb downstream of GBA1 gene. Red bar, length and location of the six long-range (LR) SMRT amplicons used in this study (primers in Table 1). Lower panel, purified LR-PCR amplicons on 0.75% agarose gel.
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References

    1. Beutler E., Grabowski G. In: The Metabolic and Molecular Bases of Inherited Disease. Scriver C., Beaudet A., Sly W., Valle D., editors. McGraw Hill; New York: 2001. The mucopolysaccharidoses; pp. 3635–3668.
    1. Grabowski G.A. Gaucher disease and other storage disorders. Hematology Am Soc Hematol Educ Program. 2012;2012:13–18. - PubMed
    1. Drelichman G., Fernández Escobar N., Basack N., et al. 2015. Actualización del consenso argentino de enfermedad de gaucher: grupo argentino para el diagnóstico y tratamiento de la enfermedad de gaucher. HEMATOLOGÍA Volumen 19 Suplemento Enfermedad de Gaucher; pp. 4–51.
    1. Murugesan V., Chuang W.L., Liu J., Lischuk A., Kacena K., Lin H., Pastores G.M., Yang R., Keutzer J., Zhang K., Mistry P.K. Glucosylsphingosine is a key biomarker of Gaucher disease. Am. J. Hematol. 2016;11:1082–1089. - PMC - PubMed
    1. Bultron G., Kacena K., Pearson D., Boxer M., Yang R., Sathe S., Pastores G., Mistry P.K. The risk of Parkinson’s disease in type 1 Gaucher disease. J. Inherit. Metab. Dis. 2010;33(2):167–173. - PMC - PubMed

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