Estudios moleculares en 59 pacientes Argentinos con Enfermedad de Gaucher. Un informe del ICGG Registro Internacional de Gaucher y del Grupo Argentino de Diagnóstico y Tratamiento de la Enfermedad de Gaucher

DRELICHMAN G; WATMAN N; ELENA GRACIELA; KOHAN REGINA; DRAGOSKY MARTA; FELIU A; CUELLO MARÌA FERNANDA; FYNN ALCIRA; ANGARONI CELIA; OLLER DE RAMIREZ ANA MARÍA; OLIVERI B; LARROUDÉ MARÍA SILVIA; MASLLORENS FRANCISCA; SZLAGO MARINA; SCHENONE ANDREA

Congreso; XX Congreso Argentino de Hematología; 2011

Molecular studies in 59 patients with Gaucher disease: a report from the International Gaucher Registry and the Argentine Group of Diagnosis and Treatment of Gaucher Disease Guillermo Drelichman 1; Nora Watman 2; Graciela Elena 3; Dra. Regina Kohan4 ; Dra. Marta Dragosky 5; Dra. Aurora Feliu 6; Dra. Maria Fernanda Cuello 7; Dra. Alcira Fynn 7 Dra. Celia Angaroni 8; Dra. Ana María Oller de Ramírez; Dra. Beatriz Oliveri 9; Dra. María Silvia Larroudé 10; Dra. Francisca María Masllorens 11; Dra. Marina Szlago12 ; Dra. Andrea B. Schenone12 Introduction: The molecular knowledge is essential for genetic counseling as well as being indispensable for the identification of carriers (autosomal recessive). There are genotype / phenotype correlations to distinguish non neuropathic of neuropathic forms: detecting at least one N370S allele excludes neurologic involvement. L444P/L444P genotype is associated with an increased risk of neuropathic disease. The glucocerebrosidase gene is located on chromosome 1q2.1 and consists of 11 exons. There are more than 300 mutations, 8 of them are the most common. Gaucher disease is one of the orphan diseases. Due to its low incidence, it´s very useful to have registries of these diseases. In 1991 the International Gaucher Registry(GR) was created and currently has the most important database of long-term monitoring for an orphan disease, with more than 5780 patients. Argentina collects information since 1992 Material and methods: The molecular studies were performed with the support of the GR. We performed PCR / enzymatic digestion of the eight most common mutations. Molecular and clinical data of patients from Argentina has been evaluated until March 2, 2011. Objectives: To evaluate the most common genotypes in our population and the correlations genotype / phenotype Results: Since 1992, 159 patients have been enrolled in GR of Argentina. Regarding the type of disease: 151 patients were type 1, 2 patients-types 2. The mean age at diagnosis was 14 years old (r 0-67 a). 92 patients (58%) were females and 67 males (42%). 59 of 159 (37%) had molecular studies. The most common genotypes were : N370S/L444P 13 (22%); N370S/Alelle rare * 13 (22%); N370S/84GG 12 (20%), N370S /? ** 5 (8%); rare allele / rare allele: 4 (7%); D409H / rare allele 4 (7%); rare allele /? 2 (3%);N370S / D409H 2 (3 %); N370S/IVS2 +1 G> A 1 (2%), L444P / L444P 1 (2%), L444P /? 1 (2%). *Rare Allele is defined as a known allele that is not N370S, L444P, IVS2 +1 G> A, D409H or 84GG. ** The analysis of the most frequent mutations was negative, so far is an unknown allele Conclusion: The most common genotypes were those with one N370S allele (83%). We found correlations genotype / phenotype to distinguish non neuropathic of neuropathic forms: our population is dominated by non-neuropathic clinical forms, 99% matching with the high frequency of alleles N370S (83%). Only 1% of patients had double-L444P allele that has relation with the low percentage of neuropathic forms (1%).