Gaucher disease is the most frequent lysosomal storage disorder due to the deficiency of the acid β-glucosidase, encoded by the GBA gene. In this study, we report the structural and functional characterization of 11 novel GBA alleles. Seven single missense alleles, P159S, N188I, E235K, P245T, W312S, S366R and W381C, and two alleles carrying in cis mutations, (N188S; G265R) and (E326K; D380N), were studied for enzyme activity in transiently transfected cells. All mutants were inactive except the P159S, which retained 15% of wild-type activity. To further characterize the alleles carrying two in cis mutations, we expressed constructs bearing singly each mutation. The presence of G265R or D380N mutations completely abolished enzyme activity, while N188S and E326K mutants retained 25 and 54% of wild-type activity, respectively. Two mutations, affecting the acceptor splice site of introns 5 (c.589-1G>A) and 9 (c.1389-1G>A), led to the synthesis of aberrant mRNA. Unpredictably, family studies showed that two alleles resulted from germline or 'de novo' mutations. These results strengthen the importance of performing a complete and accurate molecular analysis of the GBA gene in order to avoid misleading conclusions and provide a comprehensive functional analysis of new GBA mutations.

Erika Malini

Serena Grossi

Marta Deganuto

Camillo Rosano

Rossella Parini

Silvia Dominisini

Roberta Cariati

Stefania Zampieri

Bruno Bembi

Mirella Filocamo

Andrea Dardis

European journal of human genetics : EJHG

《欧洲人类遗传学杂志》是欧洲人类遗传学会的官方期刊，在快速发展的人类遗传学和基因组学领域发表高质量的原创研究论文、简短报告和评论。它涵盖分子、临床和细胞遗传学，高级生物医学研究和临床医生之间的接口，并在遗传学界弥合各种设施、资源和观点。关键领域包括：-单基因和多因素疾病-发育和畸形-遗传性癌症-医学基因组学-基因作图和功能研究-基因型-表型相关性-遗传变异和基因组多样性-统计和计算遗传学-生物信息学-诊断学进展-治疗和预防-动物模型-遗传服务-社区遗传学

The European Journal of Human Genetics is the official journal of the European Society of Human Genetics, dedicated to publishing high-quality original research papers, brief reports, and reviews in the rapidly evolving fields of human genetics and genomics. The journal covers molecular, clinical, and cytogenetics, as well as the interface between advanced biomedical research and clinical practice, aiming to bridge various facilities, resources, and perspectives within the genetics community. Key areas of focus include: single-gene and multifactorial diseases, development and malformations, hereditary cancers, medical genomics, gene mapping and functional studies, genotype-phenotype correlations, genetic variation and genomic diversity, statistical and computational genetics, bioinformatics, advancements in diagnostics, treatment and prevention, animal models, genetic services, and community genetics.

《欧洲人类遗传学杂志》是欧洲人类遗传学会的官方期刊，致力于在快速发展的遗传学和基因组学领域发表高质量的原创研究论文、简短报告和评论。期刊涵盖了分子、临床和细胞遗传学，以及高级生物医学研究与临床实践之间的交叉领域，旨在弥合遗传学界的各种设施、资源和观点。关键研究领域包括：单基因和多因素疾病、发育与畸形、遗传性癌症、医学基因组学、基因作图与功能研究、基因型与表型相关性、遗传变异与基因组多样性、统计与计算遗传学、生物信息学、诊断进展、治疗与预防、动物模型、遗传服务和社区遗传学。

European Journal of Human Genetics

Eur J Hum Genet

Functional analysis of 11 novel GBA alleles.

The structural and functional characterization of 11 novel GBA alleles is reported, showing that two alleles resulted from germline or ‘de novo’ mutations, strengthening the importance of performing a complete and accurate molecular analysis of the GBA gene in order to avoid misleading conclusions and provide a comprehensive functional analysis of new GBA mutations.

Category	Quartile
生物学	2
生物学, 生化与分子生物学	2
生物学, 遗传学	2

Functional analysis of 11 novel GBA alleles.

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Journal Info

Category	Quartile
GENETICS & HEREDITY	2