Τίτλος:
Screening for TSC1 and TSC2 mutations using NGS in Greek children with tuberous sclerosis syndrome
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Tuberous Sclerosis Complex (TSC) is a rare neurocutaneous syndrome inherited by an autosomal dominant manner. The disorder is commonly manifested by the presence of multiple benign tumors located in numerous tissues, including the brain, heart, skin and kidneys. Seizures, autism, developmental and behavioral delay, as well as non-neurological phenotypic findings, are suggestive of TSC. The identification of one pathogenic mutation in either the TSC1 or TSC2 genes is considered to be an independent diagnostic criterion. In our study, seventeen Greek patients, 2yo on average, were analyzed for the presence of pathogenic germline mutations in the aforementioned loci by Next-Generation Sequencing. A TSC1/2 gene panel was designed for the molecular diagnosis of the disease. Patients underwent initial diagnosis based on their clinical symptoms, most frequently involving the presence of skin lesions and/or epilepsy. Only one case was familial. Sixteen different genetic alterations were identified in TSC1 and TSC2 genes in fifteen patients, giving a 88% detection rate by employing NGS technology. Overall, most pathogenic mutations (11/15) identified were located in the TSC2 gene with exon 41 being the most frequent. With respect to genotype-phenotype association, no patient TSC1 (+) developed SEGA or renal cysts. No significant differences were observed between different types of TSC2 mutations and any clinical feature. Sequencing also revealed 18 different SNPs across the TSC1 and 20 across the TSC2 genes. This is the first registry of the genetic profile of TSC patients in Greece using a custom-made gene panel as molecular diagnostic tool. © 2018 European Paediatric Neurology Society
Συγγραφείς:
Papadopoulou, A.
Dinopoulos, A.
Koutsodontis, G.
Pons, R.
Vorgia, P.
Koute, V.
Vratimos, A.
Zafeiriou, D.
Περιοδικό:
European Journal of Paediatric Neurology
Εκδότης:
W.B. Saunders Ltd
Λέξεις-κλειδιά:
tuberin; tuberous sclerosis complex 1; tuberous sclerosis complex 2; unclassified drug; tuberin; tuberous sclerosis complex 1 protein; tumor suppressor protein, 3' untranslated region; angiomyolipoma; Article; autism; brain damage; child; childhood disease; clinical article; clinical feature; controlled study; electroencephalography; epilepsy; exon; female; fibroma; genetic analysis; genotype phenotype correlation; germline mutation; Greece; hamartoma; hemangiofibroma; human; indel mutation; infant; infantile spasm; intron; kidney cyst; male; molecular diagnosis; newborn; next generation sequencing; patient; priority journal; screening; seizure; single nucleotide polymorphism; skin defect; subependymal giant cell astrocytoma; tuberous sclerosis; genetics; high throughput sequencing; mutation; phenotype; preschool child; register; tuberous sclerosis, Child; Child, Preschool; Exons; Female; Greece; High-Throughput Nucleotide Sequencing; Humans; Male; Mutation; Phenotype; Registries; Tuberous Sclerosis; Tumor Suppressor Proteins
DOI:
10.1016/j.ejpn.2018.01.026
