Özet:

Aims: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy with multisystemic involvement and variable phenotypic features. A diagnosis is usually made through the clinical diagnostic criteria. However, the clinical diagnosis can be difficult due to the absence of clear phenotype-genotype correlation and overlapping findings with other ciliopathies. Next-generation sequencing (NGS) is a rapid and cost-effective diagnostic method for this group of diseases. Besides correct diagnosis, detection of novel variants also contributes to establishing new phenotype-genotype correlations and delineating the pathophysiology of the syndrome. Here, we aimed to present clinical and molecular findings of patients with BBS using NGS panel analysis to contribute to the genotype-phenotype correlation in this rare syndrome. Methods: We retrospectively reviewed the medical records of patients with a suspicion of BBS admitted to the Pediatric Genetics Department in Umraniye Training and Research Hospital. Patients who met the BBS clinical diagnostic criteria were included in the study. Targeted NGS analysis, including 20 genes associated with BBS, was performed on an Illumina Next-Seq-500 platform. Results: The final analyses included 6 patients (age, mean±standard deviation: 14.3±6.6 years, female: 50%). Rod cone dystrophy (100%), polydactyly (100%), and intellectual disability (100%) were the most common findings followed respectively by obesity (83%), renal anomalies (83%), liver anomalies (67%), dental problems (67%), metabolic problems (50%), genital anomalies (33%), psychiatric disorders (33%), and sleep apnea (33%). The 5th metatarsal shortness and camptodactyly were anomalies reported for the first time in BBS. Seven variants were detected in the BBS1, BBS7, BBS5, BBS9, and MKKS, two of which were novel. BBS7 was the most common gene. Conclusions: Our study expanded the genotypic spectrum of the disease with two novel variants reported. Besides, by defining novel/rare clinical features, including camptodactyly, the fifth metatarsal, the 4th-5th metacarpal shortness, and nephrocalcinosis, it formed a source for the phenotype-genotype correlation trying to be established in the literature.

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