GBA Gene Mutation Analysis Of 5 Cases Of Gaucher Disease

Objective: Gaucher’s disease is an autosomal recessive genetic disease,which is caused by glucocerebrosidase deficiency.The disease is caused by glucocerebrosidase(GBA)gene mutation.The common clinical symptoms are hepatosplenomegaly,anemia,thrombocytopenia and osteopathy.The quality of life of the patients is seriously reduced.In addition,a few specific gene mutations have a certain correlation with the clinical classification of patients,which can help clinicians to judge the degree of disease and prognosis,and play a guiding role in treatment.In addition,accurate genetic diagnosis,genetic counseling and prenatal diagnosis are crucial to reduce the incidence rate of the disease.We detected GBA gene mutations in five children with Gaucher disease and some of their families who were treated with enzyme replacement therapy in Tianjin.Methods: collect the peripheral blood of patients and their families,extract the genomic DNA of peripheral blood,obtain the GBA gene sequence from the human genome database and design the primers,amplify the exon by PCR,further purify it after gel recovery,detect the GBA gene mutation of patients and their families by direct sequencing,and compare the sequencing results with Gen B The sequence of bank was compared and analyzed to find out the mutation site and type of GBA gene.Results: the results of sequencing showed that there was c.475C> T(R120W)heterozygous mutation in exon 5,c.680 a A> G(N188S)heterozygous mutation in exon 6,c.1448 T > C(L4444P)homozygous mutation in exon 10,c.475 C > T(R120W)homozygous mutation in exon 5,c.1342 g G> C(D409H)homozygous mutation in exon 9.In exon 10,there are c.1448 T > C(L4444P)heterozygous mutations,both of which are inherited from parents;in exon 5,there are c.604 C > T(R163X)heterozygous mutations,in exon 9,there are c.1363 A > G(M416V)heterozygous mutations,in exon 10,there are recncil(c.1448T> C,c.1483G> C,c.1497 G > C),Two mutations of exon 10 were inherited from parents,and the mutation of exon 6 was spontaneous.Conclusion: the GBA gene mutation sites and mutation types of 5 patients were detected by further gene sequencing of the children diagnosed by glucocerebrosidase activity test.5 patients were all reported mutations,including 3 complex heterozygotes and 2 homozygotes.Although no new mutation was found,the second was pure sum mutation with c.1448T> C(L4444P).Although the clinical manifestation is type I at present,there is a high risk of developing chronic neuropathy(type III)later.Moreover,through the gene detection of parents,the carrier type was determined,and the molecular genetic basis of Gaucher’s disease was revealed,which has guiding significance for genetic consultation and prenatal diagnosis.