Genotyping and Genetic Counseling for Patients of the Joint Tuberous Sclerosis Complex Clinics at National Taiwan University Hospital
Date Issued
2012
Date
2012
Author(s)
Hsieh, Shu-Min
Abstract
Tuberous sclerosis complex (TSC[OMIM 191100])is an autosomal dominant disease with high penetrance, characterized by the presence of hamartomas in brain, kidneys, lungs and/or other multiple organ systems. The clinical manifestations include epilepsy, mental retardation, behavioral problems, skin lesions, renal problems, which often cause harm to patients physically and psychologically. Two thirds of patients are sporadic and are thought to represent de novo mutation. Approximately one in 6,000 to one in 10,000 newborns are affected by TSC. Males and females are equally susceptible to have TSC and the chance of passing it on to offspring is 50%. TSC is caused by inactivating genetic variant at either TSC1(9q34) or TSC2 (16p13) gene. About 70% to 80% of individuals who meet definite diagnostic criteria have a small identifiable TSC1 or TSC2 gene causative variant.
Genetic testing for TSC patients has many important implications, including, but not limited to, confirmation of the diagnosis, identification of the causative variants of the patient/pedigree, and genetic counseling. The results of genetic testing may be helpful for patients, family members, medical professionals and policymakers. However, there are a total of 64 exons in TSC1 and TSC2 genes, which causative variants genetic testing for TSC to be time-consuming and expensive. It is not uncommon that genetic testing is delayed because the family cannot afford the cost.
The Joint TSC Clinics at National Taiwan University Hospital was established in July 2010. A TSC patient can get access to almost all medical professionals related to his/her medical needs at a single visit, which greatly facilitate holistic health care and multi-disciplinary collaboration. The Clinics is a one-stop solution, and provide comprehensive health care for TSC patients.
The study was approved by the Institutional Review Board (IRB) of National Taiwan University Hospital. After obtaining informed consent, we collected blood samples from 47 definite and 6 possible TSC patients and their family members at the Joint Tuberous Sclerosis Complex Clinics at National Taiwan University Hospital. We performed genotyping using next-generation sequencing (NGS) (Illumina system) technology for detecting genetic variants at the TSC1 and TSC2 genes. For possible causative variants detected in the NGS experiment, we further verified the results using traditional Sanger sequencing. Sixteen patients were previously genotyped by traditional methods; we therefore made a quick comparison between the genotyping results between the new NGS method and the traditional methods. We also performed genetic counseling for 7 families during the study period.
Among the 47 patients with definite TSC diagnosis, we could identify the causative genetic variants for 34 patients (72%), a detection rate comparable with the traditional method. Among the 16 patients previously genotyped, all the results were the same, except for two patients that we identified the causative variants which had been missed using the traditional way. We found NGS to have several advantages as a genotyping tools for TSC diagnosis, including high accuracy, high speed and relatively low cost. In the future, NGS may prove to be a valuable tool for TSC genetic diagnosis. Professional genetic counseling services will also help TSC patients and families through risk prediction and disease understanding. We hope that our comprehensive TSC care system, including the genetic testing modality and genetic counseling, can help early diagnosis and multi-disciplinary treatment of TSC patients, and reduce the number of new TSC patients from known families. The insights gained from genetic study and molecular mechanism might further facilitate the progress of medical research and provide better choices for TSC treatment.
Subjects
Tuberous sclerosis complex (TSC)
TS1
TSC2
genetic test
genetic counseling
next-generation sequencing
Sanger sequencing
Type
thesis
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