Gene Mutation Study Of GLA In A Family With Fabry Disease

Object:Using molecular biology techniques analysis of a clinical diagnosis of Fabry disease familymembers of the GLA gene mutations,mutant gene for protein structure prediction, this Fabry pedigree ispossible pathogenesis, diagnosis of Fabry disease, treatment and genetic counseling provide sometheoretical basis.Methods: Through the investigation questionnaire detailed records of the clinical data of this family theFabry patient and the family Department of, to including the age of onset, the incidence symptoms, pastmedical history, a family history of, the quality of life of, etc.. Brain CT, echocardiography,electrocardiogram, and liver and kidney function, abdominal B ultrasound, blood, urine, eye and generalphysical examination, determination of dried blood of the the proband father and daughter and some familymembersα-galactosidase A （α-GalA） activity. Acquisition of family members and control peripheralintravenous anticoagulant7GLA gene was amplified exon and its adjacent areas, the amplified productswere purified and sequenced. With Chromas, clustalx, SeqMan, etc. on software than the sequencing resultsto determine the mutation site. New mutations through the HGMD and the NCBI database searches, clearthe mutation is known SNP mutations or known or have not been reported. New mutations, the NCBIHomogene website database retrieval clear change in the amino acids conserved genes in different speciesGLA, suggesting that the mutation occurred cause of protein may affect. Using DNAStar and networkservers in SWISS-MODEL prediction of protein secondary structure and tertiary structure of the GLA genemutations preliminary elucidate the pathogenesis of this Fabry pedigrees may, and to further explore therelationship between genotype and phenotype.Results:The Fabry pedigrees with a membership of26people,13were related to clinical symptoms, threemale and10female. Three male patients earlier and more severe onset.Incidence of heavy female patients,only two patients, one showed renal involvement, other severe acral pain, the remaining eight femalepatients with mild symptoms; analysis found that the clinical data of the Fabry pedigreesthe clinicalphenotype of the family classic.Its the GLA gene seven exons and the adjacent areas sequencing analysisrevealed the family share a gene mutation, located in exon5, and the type of mutation for c.717₇18delAA.Secondary and tertiary structure prediction of the mutation in the gene encoding the protein found themutation in the gene coding for the early termination of a truncated protein structure and function changes,so the of c.717₇18delAA for the family disease-causing mutation.Found two mutations in the controlpopulation, a small fragment missing in the third intron g.7188₇192delCAGCC, the other is located in thefirst exon of missense mutations G11A, G11A for new mutations, protein structure prediction, the mutationG11A protein structure is relatively small.Conclution:Mutations on protein structure and function c.717₇18delAA greater impact, which is amember of the family classic clinical manifestations consistent with pedigrees for Fabry disease-causingmutations;Pedigrees female Fabry patients with clinical symptoms vary, activity was measured withdiagnostic limitations of genetic testing for the diagnosis of Fabry disease is an important method;GLAgene intron mutation g.7188₇192delCAGCC existence of different clinical phenotypes, pending furtherstudy;G11A is a new GLA gene mutations, or disease to be studied;To improve the diagnosis of Fabrydisease awareness and the level of its relationship with the GLA gene mutation, accurate prenatal diagnosisand clinical consulting, providing genetic basis.