Consanguinity and founder effect for Gaucher disease mutation <scp>G377S</scp> in a population from Tabuleiro do Norte, Northeastern Brazil

Gaucher Disease (GD) is the most prevalent inherited lysosomal storage disorder characterized by a glucocerebroside enzyme deficiency. This enzyme is a lysosomal hydrolase that plays a role in the breakdown of the glycosphingolipid complex. In general population, this disease is rare, with an incidence of about 0.39 to 5.80 per 100.000 birth and a prevalence of about 0.70 to 1.75 per 100.000 birth. We reported a two-year-old female patient who presented with a gradual increase of abdominal circumference and gum bleeding. There is a family history of third-degree consanguinity. Physical examination showed hepatosplenomegaly, and the laboratory results revealed the presence of hyperferritinemia and pancytopenia. Bone marrow biopsy revealed Gaucher cells. The diagnosis of GD was confirmed by a low level of glucocerebrosidase activity (0.27 uM/hr) and the presence of a homozygous mutation in exon 11 (c.1448T>C) of GBA gene, indicating an autosomal recessive GD. Conclusion: Early identification through clinical and histological findings in GD is critical. Children with unexplained hyperferritinemia and hepatosplenomegaly should be suspected of GD as one of the differential diagnosis. The early diagnosis of GD is the key to effective management, such as enzyme replacement, which may decrease its morbidity.

Section: Discussionmentioning

confidence: 99%

“…GD is an autosomal recessive disorder. The recessive autosomal gene's phenotypic manifestation may emerge as a consequence of marital consanguinity over generations [4]. GD is a multiple organ chronic disorder.…”

Section: Introductionmentioning

confidence: 99%

Gaucher Disease in a Two-Year-Old Girl with Hyperferritinemia: A Case Report

Sugiharto¹,

Pratiwi²,

Sidiartha³

2022

IJGG

“…Interestingly, a few recurrent GBA mutations, including p.N409S in Ashkenazi Jewish and European communities [12], p.D448H in northern Swedish [13], p.W417G in French-Canadian [14], and p.G416S in Tabuleiro do Norte, Northeastern Brazilian [15] populations have been suggested as founder mutations.…”

Section: Introductionmentioning

confidence: 99%

The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

Choi

et al. 2020

Preprint

Background Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients. Results The study cohort included 62 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harbored the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (9%). The median age at diagnosis of the 18 patients harboring the p.G85E mutation was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3,075 years. ConclusionThe GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.

“…Interestingly, a few recurrent GBA mutations, including p.N409S in Ashkenazi Jewish and European communities [11], p.D448H in northern Swedish [12], p.W417G in French-Canadian [13], and p.G416S in Tabuleiro do Norte, Northeastern Brazilian [14] populations have been suggested as founder mutations.…”

Section: Introductionmentioning

confidence: 99%

“…1a). Among the 20 missense variants,14 pathogenic mutations, and six likely-pathogenic variants (p.V230G, p.P240H, p.R316C, p.D354E, p.N425K, and p.I442T), classi ed according to American College of Medical Genetics guidelines, were identi ed. Thirty-two patients from 30 families had neuronopathic GD, including 10 with type 2 (16%) and 22 with type 3 (35%) GD.…”

mentioning

confidence: 99%

The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects

Choi

et al. 2020

Preprint

Background Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients. Results The study cohort included 63 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harboured the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (10%). Of the 18 patients harbouring the p.G85E mutation, their median age at diagnosis was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3,075 years. Conclusion The GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.