Genetic diagnosis of a Chinese multiple endocrine neoplasia type 2A family through whole genome sequencing
| Autor: | Ju-Ming Ma, Feng Li, Xiao-Ping Qi, Zhen-Fang Du, Jian-Qiang Zhao, Peng-Fei Li, Zhi-Lie Cao |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proband Adult Male endocrine system diseases Adolescent Biology Genome General Biochemistry Genetics and Molecular Biology Pheochromocytoma 03 medical and health sciences Asian People medicine Humans Family Genetic Predisposition to Disease Multiple endocrine neoplasia Gene Genetics Whole genome sequencing Whole Genome Sequencing Genome Human Multiple Endocrine Neoplasia Genetic Variation General Medicine Middle Aged medicine.disease 030104 developmental biology Mutation (genetic algorithm) Human genome Female General Agricultural and Biological Sciences |
| Zdroj: | Journal of biosciences. 42(2) |
| ISSN: | 0973-7138 |
| Popis: | Approximately 98% of patients with multiple endocrine neoplasia type 2A (MEN 2A) have an identifiable RET mutation. Prophylactic or early total thyroidectomy or pheochromocytoma/parathyroid removal in patients can be preventative or curative and has become standard management. The general strategy for RET screening on family members at risk is to sequence the most commonly affected exons and, if negative, to extend sequencing to additional exons. However, different families with MEN 2A due to the same RET mutation often have significant variability in the clinical exhibition of disease and aggressiveness of the MTC, which implies additional genetic loci exsit beyond RET coding region. Whole genome sequencing (WGS) greatly expands the breadth of screening from genes associated with a particular disease to the whole genome and, potentially, all the information that the genome contains about diseases or traits. This is presumably due to additive effect of disease modifying factors. In this study, we performed WGS on a typical Chinese MEN 2A proband and identified the pathogenic RET p.C634R mutation. We also identified several neutral variants within RET and pheochromocytoma-related genes. Moreover, we found several interesting structural variants including genetic deletions (RSPO1, OVCH2 and AP3S1, etc.) and fusion transcripts (FSIP1-BAZ2A, etc.). |
| Databáze: | OpenAIRE |
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