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...

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Autores principales: Weiss, Karin, Kurolap, Alina, Paperna, Tamar, Mory, Adi, Steinberg, Maya, Hershkovitz, Tova, Ekhilevitch, Nina, Baris, Hagit N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rambam Health Care Campus 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115477/
https://www.ncbi.nlm.nih.gov/pubmed/30089087
http://dx.doi.org/10.5041/RMMJ.10341
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author Weiss, Karin
Kurolap, Alina
Paperna, Tamar
Mory, Adi
Steinberg, Maya
Hershkovitz, Tova
Ekhilevitch, Nina
Baris, Hagit N.
author_facet Weiss, Karin
Kurolap, Alina
Paperna, Tamar
Mory, Adi
Steinberg, Maya
Hershkovitz, Tova
Ekhilevitch, Nina
Baris, Hagit N.
author_sort Weiss, Karin
collection PubMed
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.
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spelling pubmed-61154772018-09-07 Rare Disease Diagnostics: A Single-center Experience and Lessons Learnt Weiss, Karin Kurolap, Alina Paperna, Tamar Mory, Adi Steinberg, Maya Hershkovitz, Tova Ekhilevitch, Nina Baris, Hagit N. Rambam Maimonides Med J Special Issue Celebrating the 80th Anniversary of Rambam Health Care Campus 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. Rambam Health Care Campus 2018-07-30 /pmc/articles/PMC6115477/ /pubmed/30089087 http://dx.doi.org/10.5041/RMMJ.10341 Text en Copyright: © 2018 Weiss et al. This is an open-access article. All its content, except where otherwise noted, is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Special Issue Celebrating the 80th Anniversary of Rambam Health Care Campus
Weiss, Karin
Kurolap, Alina
Paperna, Tamar
Mory, Adi
Steinberg, Maya
Hershkovitz, Tova
Ekhilevitch, Nina
Baris, Hagit N.
Rare Disease Diagnostics: A Single-center Experience and Lessons Learnt
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 Special Issue Celebrating the 80th Anniversary of Rambam Health Care Campus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115477/
https://www.ncbi.nlm.nih.gov/pubmed/30089087
http://dx.doi.org/10.5041/RMMJ.10341
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