Genetic Studies Of A Family With Congenital Hereditary Corneal Dystrophy And A Family With Mucopolysaccharidosis Type Ⅵ

Objective:The whole exome sequencing technology was used to identify the causative genes and mutation loci and to investigate the causative mechanisms in two lines with suspected hereditary corneal opacities.Methods:We collected two families with ocular manifestations of corneal opacities,family 1 containing 2 patients and 10 normal family members and family 2 containing 1 patient and 7 normal family members.A detailed ophthalmologic examinations,including slit lamp microscopy,photography of the anterior eye segment,intraocular pressure,visual acuity,and A-scan ultrasonography,were performed on the patients and the participating relatives,and their family histories and clinical signs and characteristics were analyzed.After obtaining the consent of the patients and family members and signing the relevant informed consent forms,peripheral venous blood was collected from the patients and some of his family members,and genomic DNA was extracted,and whole exome capture high-throughput sequencing technology wasused,combined with bioinformatic analysis and family co-segregation verification to screen out the causative genes and mutation loci.Results:1.After detailed ophthalmologic examinations,it was clear that both the proband and his sister had congenital hereditary corneal dystrophy in family 1,and the rest of the family members had no abnormal clinical manifestations.Genetic assessments revealed a pathogenic mutation in the SLC4A11 gene of the patients in family 1,exon 11 c.1384A>G,p.Trp462Arg,and the p.W462R mutation was firstly reported worldwide by bioinformatic analysis and all normal members of the family participated in this study were carriers.2.In family 2,in combination with the whole exome sequencing results,the proband was diagnosed as mucopolysaccharidosis type VI,and the rest of the family members had no abnormal clinical manifestations.The ARSB gene was causative gene in this patient by gene sequencing,Compound heterozygous missense mutations were found in the ARSB gene,namely c.1325G>A(p.Thr442Met)(M1)and c.1197G>C(p.Phe399Leu)(M2).Conclusion:1.In this study,we detected that the patients in family 1 had congenital hereditary corneal dystrophy with a mutation in the SLC4A11 gene,exon 11 c.1384A>G,p.Trp462Arg,and this mutation was the first report in the world.2.The causative gene of the patient in family 2 was ARSB(aryl sulfatase B)gene with two compound heterozygous mutations of c.1197G>C(p.Phe399Leu)and c.1325G>A(p.Thr442Met),and the patient was finally diagnosed with mucopolysaccharidosis typeⅥ.