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Genetic Counseling and NGS Screening for Recessive LGMD2A Families

Genetic counseling applied to limb–girdle muscular dystrophies (LGMDs) can be very challenging due to their clinical and genetic heterogeneity and the availability of different molecular assays. Genetic counseling should therefore be addressed to select the most suitable approach to increase the dia...

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Autores principales: Strafella, Claudia, Caputo, Valerio, Campoli, Giulia, Galota, Rosaria Maria, Mela, Julia, Zampatti, Stefania, Minozzi, Giulietta, Sancricca, Cristina, Servidei, Serenella, Giardina, Emiliano, Cascella, Raffaella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349198/
https://www.ncbi.nlm.nih.gov/pubmed/32397577
http://dx.doi.org/10.3390/ht9020013
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author Strafella, Claudia
Caputo, Valerio
Campoli, Giulia
Galota, Rosaria Maria
Mela, Julia
Zampatti, Stefania
Minozzi, Giulietta
Sancricca, Cristina
Servidei, Serenella
Giardina, Emiliano
Cascella, Raffaella
author_facet Strafella, Claudia
Caputo, Valerio
Campoli, Giulia
Galota, Rosaria Maria
Mela, Julia
Zampatti, Stefania
Minozzi, Giulietta
Sancricca, Cristina
Servidei, Serenella
Giardina, Emiliano
Cascella, Raffaella
author_sort Strafella, Claudia
collection PubMed
description Genetic counseling applied to limb–girdle muscular dystrophies (LGMDs) can be very challenging due to their clinical and genetic heterogeneity and the availability of different molecular assays. Genetic counseling should therefore be addressed to select the most suitable approach to increase the diagnostic rate and provide an accurate estimation of recurrence risk. This is particularly true for families with a positive history for recessive LGMD, in which the presence of a known pathogenetic mutation segregating within the family may not be enough to exclude the risk of having affected children without exploring the genetic background of phenotypically unaffected partners. In this work, we presented a family with a positive history for LGMD2A (OMIM #253600, also known as calpainopathy) characterized by compound heterozygosity for two CAPN3 mutations. The genetic specialist suggested the segregation analysis of both mutations within the family as a first-level analysis. Sequentially, next-generation sequencing (NGS) analysis was performed in the partners of healthy carriers to provide an accurate recurrence/reproductive risk estimation considering the genetic background of the couple. Finally, this work highlighted the importance of providing a genetic counseling/testing service even in unaffected individuals with a carrier partner. This approach can support genetic counselors in estimating the reproductive/recurrence risk and eventually, suggesting prenatal testing, early diagnosis or other medical surveillance strategies.
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spelling pubmed-73491982020-07-22 Genetic Counseling and NGS Screening for Recessive LGMD2A Families Strafella, Claudia Caputo, Valerio Campoli, Giulia Galota, Rosaria Maria Mela, Julia Zampatti, Stefania Minozzi, Giulietta Sancricca, Cristina Servidei, Serenella Giardina, Emiliano Cascella, Raffaella High Throughput Communication Genetic counseling applied to limb–girdle muscular dystrophies (LGMDs) can be very challenging due to their clinical and genetic heterogeneity and the availability of different molecular assays. Genetic counseling should therefore be addressed to select the most suitable approach to increase the diagnostic rate and provide an accurate estimation of recurrence risk. This is particularly true for families with a positive history for recessive LGMD, in which the presence of a known pathogenetic mutation segregating within the family may not be enough to exclude the risk of having affected children without exploring the genetic background of phenotypically unaffected partners. In this work, we presented a family with a positive history for LGMD2A (OMIM #253600, also known as calpainopathy) characterized by compound heterozygosity for two CAPN3 mutations. The genetic specialist suggested the segregation analysis of both mutations within the family as a first-level analysis. Sequentially, next-generation sequencing (NGS) analysis was performed in the partners of healthy carriers to provide an accurate recurrence/reproductive risk estimation considering the genetic background of the couple. Finally, this work highlighted the importance of providing a genetic counseling/testing service even in unaffected individuals with a carrier partner. This approach can support genetic counselors in estimating the reproductive/recurrence risk and eventually, suggesting prenatal testing, early diagnosis or other medical surveillance strategies. MDPI 2020-05-10 /pmc/articles/PMC7349198/ /pubmed/32397577 http://dx.doi.org/10.3390/ht9020013 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Strafella, Claudia
Caputo, Valerio
Campoli, Giulia
Galota, Rosaria Maria
Mela, Julia
Zampatti, Stefania
Minozzi, Giulietta
Sancricca, Cristina
Servidei, Serenella
Giardina, Emiliano
Cascella, Raffaella
Genetic Counseling and NGS Screening for Recessive LGMD2A Families
title Genetic Counseling and NGS Screening for Recessive LGMD2A Families
title_full Genetic Counseling and NGS Screening for Recessive LGMD2A Families
title_fullStr Genetic Counseling and NGS Screening for Recessive LGMD2A Families
title_full_unstemmed Genetic Counseling and NGS Screening for Recessive LGMD2A Families
title_short Genetic Counseling and NGS Screening for Recessive LGMD2A Families
title_sort genetic counseling and ngs screening for recessive lgmd2a families
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349198/
https://www.ncbi.nlm.nih.gov/pubmed/32397577
http://dx.doi.org/10.3390/ht9020013
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