Three unique base pair changes in a family with Gaucher disease

Abstract

Single-stranded cDNA was prepared from RNA obtained from a patient with type 1 Gaucher disease. The cDNA was amplified in vitro and analyzed by sequencing. Three base-pair changes were identified which included a G to C transversion at nucleotide 3119 of the active gene (Asp140----His), an A to C transversion at nucleotide 3170 (Lys157----Gln) and a G to A change at nucleotide 5309 (Glu326----Lys). To study the mode of inheritance of the three different base-pair changes, genomic DNA was prepared from blood or skin fibroblasts of several family members. Genomic glucocerebrosidase DNA sequences were amplified and subjected to hybridization with allele-specific oligonucleotides (ASOs). The hybridization profiles demonstrated that two of the base-pair changes originated from the mother and were transmitted to her two affected sons and to a grandchild, while the third base-pair change, originating from the father, was transmitted to his two affected sons, a carrier daughter and a second grandchild. Tests of other patients with Gaucher disease failed to disclose the presence of the three base-changes. This is a unique family with three base-pair changes tightly linked to Gaucher disease.

Myoclonic Epilepsy in Gaucher Disease: Genotype-Phenotype Insights from a Rare Patient Subgroup

“…Consanguinity was not reported in any of the cases. Patients 11 and 13 had other siblings with both Gaucher disease and myoclonus, whereas patient 10 had an adult brother with Gaucher disease who shared the same genotype but who lacked neurologic manifestations (44). Several of the clinical features were shared by all 16 patients and others were more variable.…”

Non–pseudogene-derived complex acid β-glucosidase mutations causing mild type 1 and severe type 2 Gaucher disease

“…In GD, the occurrence of multiple non-pseudogene-derived point mutations in a single acid β-glucosidase allele was reported only once: a D140H+E326K allele that, together with a K157Q allele, caused type 1 GD (36). Thus, the find-…”

“…Interestingly, one other complex allele containing the E326K lesion has been reported in a mild type 1 GD patient with the genotype K157Q/D140H+E326K (36). To determine if the E326K lesion was a polymorphism and the role of these non-pseudogene-derived complex alleles in the causation of these diverse phenotypes, the individual and complex mutations were expressed and characterized.…”

Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA)

“…These may arise as diseasecausing alterations in cis with polymorphisms or may represent multiple pathogenic substitution events. While initially reported as single disease-causing mutations Eyal et al, 1991], two specific alterations, c.1093G4C (E326 K) and c.1223C4T (T369 M), have been found in patients primarily in cis with other identified mutations Walker et al, 2003] and have lead to published corrections after identification of a second mutation on the same allele [Torralba et al, 2001a[Torralba et al, , 2001b. Zhao et al [2003b] reported a family in which a c.1093G4C allele was found in two unaffected individuals who carried either c.721G4A (G202R) or c.1448T4C (L444P) on their second allele.…”