The relationship between phenotype and genotype in familial hyperlipidemia cases

Aim: Aim of this dissertation study is to reveal association between demographic information, clinical features and treatment by investigating genetic mutation of the patients with primer familial hyperlipidemia. Material and Method: Demographic features, background, family history, clinic findings, treatments received and laboratory data from total 33 children and adolescent patients who consulted to policlinic follow-up between 01.08.2016 and 01.02.2017, and also diagnosed with primer familial hyperlipidemia in Gaziantep University, Medical School, Pediatric Endocrinology and Metabolism Department Polyclinic, were investigated. Patients were final diagnosed by using Frederickson and familial hypercholesterolemia classification (Simon-Broome Criterions). LDLR, ApoB100, LDLRAP1 and PCSK9 genes were scanned for frequent mutations. 5 UTR and 3 UTR regions of LDRL gene 18 exon, Apo-B 29 exon, LDLRAP1 gene 15 exon and PCSK9 gene 13 exon (except for introns) were scanned. Findings: There are 20 (60,6%) females and 13 (39,4%) males of total 33 patients. Mutation has been detected in 16 cases (48,5%) and 13 mutations (39,4%) were heterozygote and 3 (9,1%) mutations were homozygote. 14 mutations were detected as LDLR mutation and 2 of them were detected as APO-B mutation. We detected LDRL gene mutation as most frequent mutation in our familial hypercholesterolemia patient group but no PCSK-9 and LDLRAP-1 mutations were detected. In LDLR assay; two homozygote D129V in 4th exon, one homozygote W577R in 12th exon, two heterozygote D129V in 4th exon, three in 10th exon heterozygote 492, four W577R in 12th exon and two heterozygote V429M in 9th exon mutations were detected. In APO-B assay, one heterozygote R1128C in 22nd exon, one S3279G heterozygote in 26th exon mutations was detected. Mean lipid levels during diagnosis of mutation positive patients in the study were detected as T-K; 323,5, LDL-K; 256, HDL-K; 256, HDL-K, 43, TG; 93 mg/dl. Last average lipid levels of patients were found as T-K; 263, LDL-K; 151, HDL-K; 42, TG; 140 mg/dl. 5 patients (31%) from mutation positive 16 patients had hypertension, 1 (6.6%) patients showed insulin resistance, 10 patients (48%) had Vit D deficiency, 9 patients (56.2%) showed osteopenia and 2 patients (12.5%) had osteoporosis. Result: Sequence analysis that includes LDL-R, ApoB-100, PCSK9 and LDLRAP1 genes is required for the genetic etiology of patients with familial hyperlipidemia. Different genetic mutations may effect the clinic picture of the disease and response to treatment in various levels. Therefore, further studies that include wide populations are needed. Key words: Familial hyperlipidemia, LDLR, PCSK9, Apo-B100, LDLRAP1