GBA1 variants in Brazilian Gaucher disease patients

Suelen Porto Basgalupp; Vivian Altmann; Filippo Pinto E Vairo; Ida Vanessa Doederlein Schwartz; Marina Siebert; MilitaoBrazilian Collaborative Group on Gaucher Disease

doi:10.1016/j.ymgmr.2023.101006

GBA1 variants in Brazilian Gaucher disease patients

Mol Genet Metab Rep. 2023 Sep 9:37:101006. doi: 10.1016/j.ymgmr.2023.101006. eCollection 2023 Dec.

Authors

Suelen Porto Basgalupp^{1

2}, Vivian Altmann², Filippo Pinto E Vairo³, Ida Vanessa Doederlein Schwartz^{2

4

5}, Marina Siebert^{2

6

7}; MilitaoBrazilian Collaborative Group on Gaucher Disease

Collaborators

MilitaoBrazilian Collaborative Group on Gaucher Disease:
Renata Cravo⁸, Erlane M Ribeiro⁹, Augusto C Dos Santos⁹, Louise L de Camargo Pinto¹⁰, Carolina C Militão¹¹, Luiz Fernando Andrade⁹

Affiliations

¹ Hospital Moinhos de Vento, Porto Alegre, RS, Brazil.
² Basic Research and Advanced Investigations in Neurosciences Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
³ Department of Clinical Genomics and Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
⁴ Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
⁵ Department of Genetics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
⁶ Postgraduate Program in Sciences of Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
⁷ Unit of Laboratorial Research, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
⁸ State Institute of Haematology "Arthur de Siqueira Cavalcanti", Rio de Janeiro, Brazil.
⁹ Albert Sabin Children's Hospital, Fortaleza, Ceará, Brazil.
¹⁰ Hospital Infantil Joana de Gusmão, Florianópolis, Brazil.
¹¹ Fundação de Hematologia e Hemoterapia de Pernambuco, Recife, Brazil.

Abstract

Gaucher disease (GD) is an autosomal recessive lysosomal disorder caused by pathogenic variants in GBA1 which result in the deficient activity of glucocerebrosidase (GCase). There are few data on the genetic characterization of Brazilian GD patients. This study aimed at characterizing the genotype of 72 unrelated Brazilian GD patients (type I = 63, type II = 4, type III = 5; male = 31). Forty patients were from South Brazil (SB), and 32 were from other regions of Brazil (Others). The exons and exon/intron junctions of GBA1 were analyzed by Sanger sequencing in 8 patients, or by massive parallel sequencing followed by Sanger of exons 9 and 10 in 64 patients. In total, 31 pathogenic variants were identified. The most frequent allele found was N370S (p.(Asn409Ser)) (41.0%), and the most frequent genotype was N370S/RecNciI p.[Asn409Ser];[Leu483Pro;Ala495Pro;Val499=](23.6%). Three variants (N370S - in exon 9, and RecNciI and L444P (p.(Leu483Pro), in exon 10) correspond to 76.3% of total alleles in SB and 59.4% in Others. Two novel variants were described: c.326del(p.(Gln109Argfs*9)) and c.690G>A (p.(?)). Although sequencing all the exons of GBA1 is the gold-standard method for the genetic analysis of GD patients, a step analysis can be proposed for Brazilian patients, starting with analysis of exons 9 and 10. The N370S allele is the most frequently associated with GD in Brazil.

Keywords: Allele frequency; Brazilian patients; GBA1; Gaucher disease; Mutations.