Clinical and molecular genetic analysis of six patients with GM1 gangliosidosis

Abstract

Objective To analyze the clinical and molecular genetic features in 6 pedigrees with GM1 ganglio-sidosis. Methods Clinical data of 6 patients with GM1 gangliosidosis were collected from April 2014 to August 2015 in Department of Pediatrics, Peking University First Hospital.Lysosomal enzyme assays for examining its activity in white blood cell were used to analyze clinical characteristics.Lysosomal enzyme assays were used to examine the mutation of β-galactosidase-1(GLB1). Polymerase chain reaction (PCR) and Sanger sequencing were used to detect GLB1 mutations to analyze the genetic characteristics. Results (1) Clinical characteristics: all 6 patients showed their initial symptoms before 8 months old.Developmental retardation and regression were seen in all patients.Startle response, epilepsy, hypotonia were found in most patients, and hearing and visual loss, Mongolian spots, hepatomegaly and growth delay were found as well.Hypomyelination was found in all 6 patients′ cranial MRI.Four cases of T2WI hyperintensity in thalami and 4 cases of cerebral and/or cerebellar atrophy were seen as well.Activity of GLB in all 6 patients decreased.Three patients were diagnosed with GM1 gangliosidosis type Ⅰ while 3 patients were GM1 gangliosidosis type Ⅱ.(2) Genetic characteristics: 10 GLB1 mutations of c. 520T>C(p.Y174H), c.622C>T(p.R208C), c.550C>T(p.Q184X), c.446C>T(p.S149F), c.266 A>G(p.H89R), c.601C>T(p.R201C), c.148T>A(p.Y50N), c.618delC(p.R208AfsX21), c.1343A>T(p.D448V), c.410C>A(p.A137D) were detected in total, including 5 novel mutations: c.550C>T(p.Q184X), c.148T>A(p.Y50N), c.618delC(p.R208AfsX21), c.266T>C(p.H89R) and c. 410C>A(p.A137D); GLB1 mutations in 4 patients were compound heterozygous while the other 2 were homozygous, and all were inherited from their healthy parents. Conclusions Six patients were diagnosed with GM1 gangliosidosis clinically and genetically.Five novel GLB1 mutations were detected in this research, expanding the spectrum of GLB1 mutations.This research will provide correct genetic counseling and prenatal diagnosis for the patients′ families as well. Key words: GM1 gangliosidosis; Beta-galactosidase; Mutation