Alport sendromu ile ilişkili genlere ait varyasyonların yeni nesil dizileme (YND) metodu ile incelenmesi

Abstract

Alport syndrome (AS) is a hereditary nephritis, characterized by sensorineural hearing loss and different eye changes sometimes observed in progressive cases. It was first reported in the early 1900s. It is a syndrome that is considered in terms of the examination and evaluation of kidney diseases, and it is a syndrome that has been extensively researched and published. In general, the diagnosis of this syndrome is based on clinical signs and careful examination of family members and electron microscopic evaluation of basement membrane structure. The disease is mainly X-linked dominant. However, autosomal recessive AS and autosomal dominant AS constitute approximately 15% and 20% of the cases, respectively. Although the prevalence of the disease in the general population is not clear, it is estimated to be around 1/10000-50000. Alport syndrome is caused by pathogenic variations in the COL4A3, COL4A4 and COL4A5 genes encoding the α3, α4 and α5 chains of type IV collagen, one of the main components of the basement membrane. In this study, which included 125 adult and pediatric patients who were born in different parts of Turkey and applied to the genetic clinic with the suspicion of AS, 16 the clinical findings and genetic results of the patients were analyzed. The mean age of the patients at the first evaluation was calculated as 23.05±20 years (3-63 years). Of the patients included in the study, 61 (48.8%) were female and 64 (51.2%) were male, with a female/male ratio of 0.95. The most common finding in patients was hematuria, followed by proteinuria. Hearing loss was detected in 18 patients. Renal diseases were observed in 45 patients. However, no variation thought to be clinically relevant was found in all patients. A single gene or digenic variation was found that could explain the clinic of 27 patients. In 16 patients, variation of uncertain clinical significance (VUS) was detected. It was recommended that 82 patients with no variation be evaluated for other syndromes or diseases similar to AS. It was recommended to evaluate 82 patients whose variation could not be detected in terms of other syndromes or diseases similar to AS. Some genetic disease groups show AS-like clinic. These 85 patients without clinically related variations in AS-related genes are estimated to be associated with these diseases, as they have clinics similar to Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly, Fabry disease, Alport-like glomerulonephritis, MYH9 gene variations, and Sebastian syndromes. These patients are needed to be re-evaluated with further examination for other possible diseases. As a result of the new generation sequencing analysis of 125 patients in this study; A total of 103 variations were detected, including 50 missense, 8 deletion/duplication, 17 splice region mutations (+-20 base), 3 3'UTR and 25 synonymous variations. 21 of these variations were pathogenic/likely pathogenic, 17 were of VUS, and 63 were found to be benign /likely benign. 33 of these 103 variations were determined as novel variations.