title: Rare familial TSC2 gene mutation associated with atypical phenotype presentation of Tuberous Sclerosis Complex.
abstract: Tuberous sclerosis complex (TSC) is a neurocutaneous disorder that results from mutations within either the TSC1 gene or the TSC2 gene. Diagnosis is based on well-established clinical criteria or genetic criteria. We describe an 18-month-old boy who presented with seizures and a single hypopigmented macule. He did not meet consensus criteria for the clinical diagnosis of TSC. Exome sequencing revealed a heterozygous TSC2 mutation (c.5138G>A (p.Arg1713His)) in the patient. This heterozygous alteration was detected in his mother as well as several other maternal family members. The mother and other family members with the mutation were asymptomatic except for the presence of hypopigmented macules. The phenotypic characteristics of the individuals in this family were not suggestive of a TSC2 mutation as none satisfied the clinical criteria for even a diagnosis of possible TSC. This case provides evidence for a unique TSC2 mutation that resulted in an atypical clinical presentation and indicates potential shortcomings of the current diagnostic criteria for TSC. These findings may have implications for genetic counseling and screening. © 2017 Wiley Periodicals, Inc.
authors.affiliation: New York State/American Program, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Jonah
authors.initials: J
authors.lastname: Fox
authors.affiliation: Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Ben-Shachar
authors.affiliation: Pediatric Neurology Unit, Tel Aviv Sourasky Medical Center, Dana-Dwek Children's Hospital, Tel Aviv, Israel.
authors.forename: Shimrit
authors.initials: S
authors.lastname: Uliel
authors.affiliation: Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ran
authors.initials: R
authors.lastname: Svirsky
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Pediatric Neurology Unit, Tel Aviv Sourasky Medical Center, Dana-Dwek Children's Hospital, Tel Aviv, Israel.
authors.forename: Aviva
authors.initials: A
authors.lastname: Fattal-Valevski
mesh_terms: D000483:Alleles; D015415:Biomarkers; D004252:DNA Mutational Analysis; D003952:Diagnostic Imaging; D004569:Electroencephalography; D056726:Genetic Association Studies; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D014402:Tuberous Sclerosis / Q000175:diagnosis* / Q000235:genetics*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D015415:Biomarkers; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
keywords: TSC2; missense mutations; tuberous sclerosis complex; variable expression