Study Reports Two Novel Mutations of Gaucher Disease Type 1

Study Reports Two Novel Mutations of Gaucher Disease Type 1

A team of researchers led by the University of Victoria, British Columbia, have recently identified two novel mutation sites characteristic of Gaucher Disease Type 1 (GD1).

The findings, “Identification of novel splice site mutation IVS9 + 1(G > A) and novel complex allele G355R/R359X in Type 1 Gaucher patients heterozygous for mutation N370S,” were published in Meta Gene.

GD, with its three main types (Type 1, 2, 3 GD) and an overall prevalence of 1/100,000, is a condition characterized by accumulated lipid substrate glucocerebroside in the reticuloendothelial cells due to a defective enzyme called glucocerebrosidase.

The impairment is caused by genetic mutations; more than 350 different mutations have been reported to date. Each of the mutations potentially affect the disease manifestation, severity, and response to therapies.

According to the report, researchers discovered two new mutations in two different patients with GD1. The patients were one male (age 3) and one female (age 20) who were diagnosed with GD through a bone biopsy. As symptoms progressed, they were referred to a medical center where they were medically accessed through blood analyses and their genomes were sequenced.

The results showed two novel mutations sites in the patients. The first one relies on splice site mutation (IVS9 + 1G > A), a genetic mutation capable of inserting, deleting or changing a number of nucleotides in a particular site. The second consists of a complex allele (cis) G355R/R359X, a variant type of  gene because some genes contain different forms situated at the same position.

The molecular structures of both identified mutations have been studied and clarified to help future identification in GD patients. The data noted that both patients carry a variant of N370S, the most prevalent mutation seen in GD patients. This gene variant adjusted the disease expression to GD1. Both patients are heterozygous for N370S.

The study concluded: “We have also developed a RFLP procedure that utilizes Hph1 restriction endonuclease digest for confirmation and efficient identification of the IVS9 + 1 mutation in future patients. In silico analysis of these novel Gaucher alleles showed that they are detrimental to either GBA splicing and/or structure and function. However, compound heterozygosity with mutation N370S in both patients has modulated the clinical expression to a mild to moderate Type 1 Gaucher phenotype.”

Discovery of novel mutations could offer new insights into the disease mechanisms, the role of glucocerebrosidase structure-function in the development of GD, and impact of therapies.

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