Genotypes and phenotypes in 20 Chinese patients with type 2 Gaucher disease

Abstract Background Gaucher disease (GD) is one of the most common lysosomal storage diseases resulting from a deficiency of glucocerebrosidase. Three main types have been described, with type 2 being the most rare and severe form. Here we investigated the clinical symptoms and mutation spectrum in 20 unrelated type 2 GD patients. Method The diagnosis of GD was based on the acid β-glucocerebrosidase (GBA) enzyme activity and direct sequencing of the GBA gene. GBA activity was measured in leukocytes and the GBA gene was amplified by a polymerase chain reaction (PCR). For patient 7, the GBA gene was analyzed by PCR as well as quantitative real-time PCR. Results The age of onset was under 12 months for all patients. All patients experienced severe neurological involvement. A total of 19 different GBA gene mutations were identified, including 6 novel mutations: two were exonic point mutations, c.1127T > C (p.Phe376Ser), c.1418T > G (p.Val473Gly); one was splicing error, ISV7-1G > C; one was insertion, c.717_718insACAG; and the other two were a gross deletion that involved exon 6 and a recombinant allele. The most prevalent mutation was Leu483Pro, which constituted 42.5% of all mutant alleles and was associated with a neurological form in Chinese GD patients as calculated by a Fisher’s exact test. Conclusion The clinical characteristics of Chinese type 2 GD were consistent with reports from other ethnic populations. We identified 6 novel mutations that contribute to the spectrum of GBA gene mutations. Our study confirmed that GD patients with the Leu483Pro allele were prone to experience neurological symptoms.