Genetic and phenotypic characteristics of 3 patients with limb-girdle muscular dystrophy: experience in a medical center in Mexico
Abstract Introduction Limb-girdle muscular dystrophy (LGMD) is a heterogeneous group of genetically inherited muscular disorders. Due to the inherent phenotypic variation among different LGMD forms, clinical diagnosis remains challenging. Guidelines recommend targeted sequencing based on the clinica...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2025-03-01
|
| Series: | Egyptian Journal of Medical Human Genetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s43042-025-00685-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849389987089350656 |
|---|---|
| author | Valentina Martínez-Montoya Alejandro Martínez-Herrera Oscar Mancera-Páez Alberto Hidalgo-Bravo María R. Rivera-Vega |
| author_facet | Valentina Martínez-Montoya Alejandro Martínez-Herrera Oscar Mancera-Páez Alberto Hidalgo-Bravo María R. Rivera-Vega |
| author_sort | Valentina Martínez-Montoya |
| collection | DOAJ |
| description | Abstract Introduction Limb-girdle muscular dystrophy (LGMD) is a heterogeneous group of genetically inherited muscular disorders. Due to the inherent phenotypic variation among different LGMD forms, clinical diagnosis remains challenging. Guidelines recommend targeted sequencing based on the clinical characteristics of the disease. However, literature regarding the genotypic and phenotypic characterization of LGMD in Mexico is limited. We aimed to characterize a group of patients with an LGMD diagnosis at our center. Methods Patients exhibiting clinical features consistent with LGMD and a high probability of the condition based on the ALDA score were selected. Genomic DNA was extracted, and next-generation sequencing (NGS) was performed using a 10-gene panel. Detected variants were confirmed via Sanger sequencing and classified according to the American College of Medical Genetics and Genomics criteria. Results Twenty patients were included in the study. LGMD R2 DYSF-related was confirmed in two patients, while LGMD R1 CAPN3-related was confirmed in one patient. A novel pathogenic frameshift variant was detected in CAPN3. Two additional patients displayed an LGMD phenotype but could not be genetically confirmed: One was heterozygous for a variant of uncertain significance in DYSF, while the other was heterozygous for a pathogenic variant in DYSF. In the confirmed LGMD cases, the ALDA software accurately included the definitive diagnosis among its predictions. Conclusion We confirmed and characterized two cases of LGMD R2 DYSF-related and one case of LGMD R1 CAPN3-related among 20 patients with muscular dystrophy. Additionally, we identified a novel pathogenic frameshift variant in CAPN3. This study expands the genetic and phenotypic landscape of LGMD in Mexican patients. |
| format | Article |
| id | doaj-art-b9873fa7f63540d082409f462ffd1f27 |
| institution | Kabale University |
| issn | 2090-2441 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Journal of Medical Human Genetics |
| spelling | doaj-art-b9873fa7f63540d082409f462ffd1f272025-08-20T03:41:47ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412025-03-012611910.1186/s43042-025-00685-9Genetic and phenotypic characteristics of 3 patients with limb-girdle muscular dystrophy: experience in a medical center in MexicoValentina Martínez-Montoya0Alejandro Martínez-Herrera1Oscar Mancera-Páez2Alberto Hidalgo-Bravo3María R. Rivera-Vega4Instituto de Oftalmología Conde ABC Santa FeDivisión de Investigación, Facultad de Medicina UNAMDepartamento de Neurología, Facultad de Medicina, Universidad Nacional de ColombiaServicio de Genética y Medicina Genómica, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”División de Investigación, Facultad de Medicina UNAMAbstract Introduction Limb-girdle muscular dystrophy (LGMD) is a heterogeneous group of genetically inherited muscular disorders. Due to the inherent phenotypic variation among different LGMD forms, clinical diagnosis remains challenging. Guidelines recommend targeted sequencing based on the clinical characteristics of the disease. However, literature regarding the genotypic and phenotypic characterization of LGMD in Mexico is limited. We aimed to characterize a group of patients with an LGMD diagnosis at our center. Methods Patients exhibiting clinical features consistent with LGMD and a high probability of the condition based on the ALDA score were selected. Genomic DNA was extracted, and next-generation sequencing (NGS) was performed using a 10-gene panel. Detected variants were confirmed via Sanger sequencing and classified according to the American College of Medical Genetics and Genomics criteria. Results Twenty patients were included in the study. LGMD R2 DYSF-related was confirmed in two patients, while LGMD R1 CAPN3-related was confirmed in one patient. A novel pathogenic frameshift variant was detected in CAPN3. Two additional patients displayed an LGMD phenotype but could not be genetically confirmed: One was heterozygous for a variant of uncertain significance in DYSF, while the other was heterozygous for a pathogenic variant in DYSF. In the confirmed LGMD cases, the ALDA software accurately included the definitive diagnosis among its predictions. Conclusion We confirmed and characterized two cases of LGMD R2 DYSF-related and one case of LGMD R1 CAPN3-related among 20 patients with muscular dystrophy. Additionally, we identified a novel pathogenic frameshift variant in CAPN3. This study expands the genetic and phenotypic landscape of LGMD in Mexican patients.https://doi.org/10.1186/s43042-025-00685-9Limb-girdle muscular dystrophyDYSFCAPN3Genetic variantCharacterization |
| spellingShingle | Valentina Martínez-Montoya Alejandro Martínez-Herrera Oscar Mancera-Páez Alberto Hidalgo-Bravo María R. Rivera-Vega Genetic and phenotypic characteristics of 3 patients with limb-girdle muscular dystrophy: experience in a medical center in Mexico Egyptian Journal of Medical Human Genetics Limb-girdle muscular dystrophy DYSF CAPN3 Genetic variant Characterization |
| title | Genetic and phenotypic characteristics of 3 patients with limb-girdle muscular dystrophy: experience in a medical center in Mexico |
| title_full | Genetic and phenotypic characteristics of 3 patients with limb-girdle muscular dystrophy: experience in a medical center in Mexico |
| title_fullStr | Genetic and phenotypic characteristics of 3 patients with limb-girdle muscular dystrophy: experience in a medical center in Mexico |
| title_full_unstemmed | Genetic and phenotypic characteristics of 3 patients with limb-girdle muscular dystrophy: experience in a medical center in Mexico |
| title_short | Genetic and phenotypic characteristics of 3 patients with limb-girdle muscular dystrophy: experience in a medical center in Mexico |
| title_sort | genetic and phenotypic characteristics of 3 patients with limb girdle muscular dystrophy experience in a medical center in mexico |
| topic | Limb-girdle muscular dystrophy DYSF CAPN3 Genetic variant Characterization |
| url | https://doi.org/10.1186/s43042-025-00685-9 |
| work_keys_str_mv | AT valentinamartinezmontoya geneticandphenotypiccharacteristicsof3patientswithlimbgirdlemusculardystrophyexperienceinamedicalcenterinmexico AT alejandromartinezherrera geneticandphenotypiccharacteristicsof3patientswithlimbgirdlemusculardystrophyexperienceinamedicalcenterinmexico AT oscarmancerapaez geneticandphenotypiccharacteristicsof3patientswithlimbgirdlemusculardystrophyexperienceinamedicalcenterinmexico AT albertohidalgobravo geneticandphenotypiccharacteristicsof3patientswithlimbgirdlemusculardystrophyexperienceinamedicalcenterinmexico AT mariarriveravega geneticandphenotypiccharacteristicsof3patientswithlimbgirdlemusculardystrophyexperienceinamedicalcenterinmexico |