Genetic Analyses of the NF1 Gene in Turkish Neurofibromatosis Type I Patients and Definition of three Novel Variants.

Neurofibromatosis Type I (NF1) is a multi systemic autosomal dominant neurocutaneous disorder predisposing patients to have benign and/or malignant lesions predominantly of the skin, nervous system and bone. Loss of function mutations or deletions of the NF1 gene is responsible for NF1 disease. Involvement of various pathogenic variants, the size of the gene and presence of pseudogenes makes it difficult to analyze. We aimed to report the results of 2 years of multiplex ligation-dependent probe amplification (MLPA) and next generation sequencing (NGS) for genetic diagnosis of NF1 applied at our genetic diagnosis center. The MLPA, semiconductor sequencing and Sanger sequencing were performed in genomic DNA samples from 24 unrelated patients and their affected family members referred to our center suspected of having NF1. In total, three novel and 12 known pathogenic variants and a whole gene deletion were determined. We suggest that next generation sequencing is a practical tool for genetic analysis of NF1. Deletion/duplication analysis with MLPA may also be helpful for patients clinically diagnosed to carry NF1 but do not have a detectable mutation in NGS.

Von Hippel-Lindau disease: the clinical manifestations and genetic analysis results of two cases from a single family.

von Hippel-Lindau (VHL) disease is an autosomal dominant inherited multi systemic cancer syndrome that is classically associated with neoplasms in multiple organs, and caused by mutations in the VHL gene on chromosome 3p25-p26. Retinal hemangioblastoma (RH) is the most frequent and the earliest clinical sign of the disease, which is seen in 40.0-60.0% of patients. In recent years, studies of patients with VHL tried to put forward the relationship between genotype and phenotype. In this study, two VHL cases in the same family with clinical findings and genetic analysis results are presented. As a consequence of the genetic studies, a heterozygous missense mutation c.202 T>C, p.S68P (Ser68Pro) in exon 1 of the VHL gene that is mapped to chromosome 3p25.3, was found in the patients' DNA sample. The germline mutation of [c.202T>C, p.S68P (Ser68Pro)] that was detected in both cases, has been reported in only two cases in the literature. However, in these reported cases, any systemic involvement except RH, were not reported. Although our cases had the same mutation, we detected renal involve-ment in both cases, and also central nervous system (CNS) involvement in one case, in addition to RH.