Rare Disease Diagnostics: A Single-center Experience and Lessons Learnt
Objective: The growing availability of next-generation sequencing technologies has revolutionized medical genetics, facilitating discovery of causative genes in numerous Mendelian disorders. Nevertheless, there are still many undiagnosed cases. We report the experience of the Genetics Institute at R...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Rambam Health Care Campus
2018-07-01
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| Series: | Rambam Maimonides Medical Journal |
| Subjects: | |
| Online Access: | https://www.rmmj.org.il/issues/38/871/manuscript |
| _version_ | 1828375019070160896 |
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| author | Karin Weiss Alina Kurolap Tamar Paperna Adi Mory Maya Steinberg Tova Hershkovitz Nina Ekhilevitch Hagit N. Baris |
| author_facet | Karin Weiss Alina Kurolap Tamar Paperna Adi Mory Maya Steinberg Tova Hershkovitz Nina Ekhilevitch Hagit N. Baris |
| author_sort | Karin Weiss |
| collection | DOAJ |
| description | Objective: The growing availability of next-generation sequencing technologies has revolutionized medical genetics, facilitating discovery of causative genes in numerous Mendelian disorders. Nevertheless, there are still many undiagnosed cases. We report the experience of the Genetics Institute at Rambam Health Care Campus in rare disease diagnostics using whole-exome sequencing (WES).
Methods: Phenotypic characterization of patients was done in close collaboration with referring physicians. We utilized WES analysis for diagnosing families suspected for rare genetic disorders. Bioinformatic analysis was performed in-house using the Genoox analysis platform.
Results: Between the years 2014 and 2017, we studied 34 families. Neurological manifestations were the most common reason for referral (38%), and 55% of families were consanguineous. A definite diagnosis was reached in 21 cases (62%). Four cases (19%) were diagnosed with variants in novel genes. In addition, six families (18%) had strong candidate novel gene discoveries still under investigation. Therefore, the true diagnosis rate is probably even higher. Some of the diagnoses had a significant impact such as alerting the patient management and providing a tailored treatment.
Conclusions: An accurate molecular diagnosis can set the stage for improved patient care and provides an opportunity to study disease mechanisms, which may lead to development of tailored treatments. Data from our genetic research program demonstrate high diagnostic and novel disease-associated or causative gene discovery rates. This is likely related to the unique genetic architecture of the population in Northern Israel as well as to our strategy for case selection and the close collaboration between analysts, geneticists, and clinicians, all working in the same hospital. |
| first_indexed | 2024-04-14T07:41:00Z |
| format | Article |
| id | doaj.art-03b86d61a4954d5c93187820253128e8 |
| institution | Directory Open Access Journal |
| issn | 2076-9172 |
| language | English |
| last_indexed | 2024-04-14T07:41:00Z |
| publishDate | 2018-07-01 |
| publisher | Rambam Health Care Campus |
| record_format | Article |
| series | Rambam Maimonides Medical Journal |
| spelling | doaj.art-03b86d61a4954d5c93187820253128e82022-12-22T02:05:29ZengRambam Health Care CampusRambam Maimonides Medical Journal2076-91722018-07-0193e001810.5041/RMMJ.10341Rare Disease Diagnostics: A Single-center Experience and Lessons LearntKarin Weiss0Alina Kurolap1Tamar Paperna2Adi Mory3Maya Steinberg4Tova Hershkovitz5Nina Ekhilevitch6Hagit N. Baris7The Genetics Institute, Rambam Health Care Center, Haifa, IsraelThe Genetics Institute, Rambam Health Care Center, Haifa, Israel and The Ruth and Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, IsraelThe Genetics Institute, Rambam Health Care Center, Haifa, IsraelThe Genetics Institute, Rambam Health Care Center, Haifa, IsraelThe Genetics Institute, Rambam Health Care Center, Haifa, IsraelThe Genetics Institute, Rambam Health Care Center, Haifa, IsraelThe Genetics Institute, Rambam Health Care Center, Haifa, IsraelThe Genetics Institute, Rambam Health Care Center, Haifa, Israel and The Ruth and Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, IsraelObjective: The growing availability of next-generation sequencing technologies has revolutionized medical genetics, facilitating discovery of causative genes in numerous Mendelian disorders. Nevertheless, there are still many undiagnosed cases. We report the experience of the Genetics Institute at Rambam Health Care Campus in rare disease diagnostics using whole-exome sequencing (WES). Methods: Phenotypic characterization of patients was done in close collaboration with referring physicians. We utilized WES analysis for diagnosing families suspected for rare genetic disorders. Bioinformatic analysis was performed in-house using the Genoox analysis platform. Results: Between the years 2014 and 2017, we studied 34 families. Neurological manifestations were the most common reason for referral (38%), and 55% of families were consanguineous. A definite diagnosis was reached in 21 cases (62%). Four cases (19%) were diagnosed with variants in novel genes. In addition, six families (18%) had strong candidate novel gene discoveries still under investigation. Therefore, the true diagnosis rate is probably even higher. Some of the diagnoses had a significant impact such as alerting the patient management and providing a tailored treatment. Conclusions: An accurate molecular diagnosis can set the stage for improved patient care and provides an opportunity to study disease mechanisms, which may lead to development of tailored treatments. Data from our genetic research program demonstrate high diagnostic and novel disease-associated or causative gene discovery rates. This is likely related to the unique genetic architecture of the population in Northern Israel as well as to our strategy for case selection and the close collaboration between analysts, geneticists, and clinicians, all working in the same hospital.https://www.rmmj.org.il/issues/38/871/manuscriptConsanguinitypersonalized medicinerare genetic diseasewhole-exome sequencing |
| spellingShingle | Karin Weiss Alina Kurolap Tamar Paperna Adi Mory Maya Steinberg Tova Hershkovitz Nina Ekhilevitch Hagit N. Baris Rare Disease Diagnostics: A Single-center Experience and Lessons Learnt Rambam Maimonides Medical Journal Consanguinity personalized medicine rare genetic disease whole-exome sequencing |
| title | Rare Disease Diagnostics: A Single-center Experience and Lessons Learnt |
| title_full | Rare Disease Diagnostics: A Single-center Experience and Lessons Learnt |
| title_fullStr | Rare Disease Diagnostics: A Single-center Experience and Lessons Learnt |
| title_full_unstemmed | Rare Disease Diagnostics: A Single-center Experience and Lessons Learnt |
| title_short | Rare Disease Diagnostics: A Single-center Experience and Lessons Learnt |
| title_sort | rare disease diagnostics a single center experience and lessons learnt |
| topic | Consanguinity personalized medicine rare genetic disease whole-exome sequencing |
| url | https://www.rmmj.org.il/issues/38/871/manuscript |
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