Variability in Disease Severity in Siblings With Homozygous Missense Variant of ADSSL1: Clinical Genetic Study and Review of Literatures

ABSTRACT Background Distal myopathies are genetic muscle disorders caused by mutations in various genes. A study found that mutations in adenylosuccinate synthetase‐like 1 (ADSSL1) are associated with distal myopathy in nine patients from six unrelated families in South Korea. Previous research show...

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Main Authors: Hui Wang, Ting Zhang, Yanming Xu, Wenhui Fan
Format: Article
Language:English
Published: Wiley 2024-11-01
Series:Molecular Genetics & Genomic Medicine
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Online Access:https://doi.org/10.1002/mgg3.70041
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author Hui Wang
Ting Zhang
Yanming Xu
Wenhui Fan
author_facet Hui Wang
Ting Zhang
Yanming Xu
Wenhui Fan
author_sort Hui Wang
collection DOAJ
description ABSTRACT Background Distal myopathies are genetic muscle disorders caused by mutations in various genes. A study found that mutations in adenylosuccinate synthetase‐like 1 (ADSSL1) are associated with distal myopathy in nine patients from six unrelated families in South Korea. Previous research showed that affected individuals experienced distal muscle weakness starting in adolescence, along with mild facial muscle weakness, slightly elevated or normal serum creatine kinase (CK) levels, and the presence of a few rimmed vacuoles in muscle fibers or minimal chronic myopathic damage. Previously reported patients in this category exhibited an early age of symptom onset and severe muscle weakness. In this study, we present a case of two sisters who share the same mutation locus but display distinct disease phenotypes. Methods A literature review was conducted on distal myopathies in patients with ADSSL1 mutations, alongside a retrospective analysis of disease severity variability among siblings with a homozygous missense variant of ADSSL1. Results The study focuses on two sisters with differing disease manifestations despite carrying the same genetic mutation. The older sister showed lower ability in running and jumping compared to her peers at age 7 and experienced notable muscle weakness and atrophy by age 27, whereas the younger sister remained free of symptoms at age 30. Conclusion These findings suggest that mutations at the same locus can result in varying disease outcomes, emphasizing the complexity of predicting disease progression based solely on genetic mutations.
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spelling doaj-art-767c78e3fee34cb1a100e23c02fb576a2025-08-20T02:27:57ZengWileyMolecular Genetics & Genomic Medicine2324-92692024-11-011211n/an/a10.1002/mgg3.70041Variability in Disease Severity in Siblings With Homozygous Missense Variant of ADSSL1: Clinical Genetic Study and Review of LiteraturesHui Wang0Ting Zhang1Yanming Xu2Wenhui Fan3Department of Neurology Sichuan Taikang Hospital Chengdu Sichuan ChinaDepartment of Neurology Sichuan Taikang Hospital Chengdu Sichuan ChinaDepartment of Neurology West China Hospital, Sichuan University Chengdu Sichuan ChinaDepartment of Neurology Sichuan Taikang Hospital Chengdu Sichuan ChinaABSTRACT Background Distal myopathies are genetic muscle disorders caused by mutations in various genes. A study found that mutations in adenylosuccinate synthetase‐like 1 (ADSSL1) are associated with distal myopathy in nine patients from six unrelated families in South Korea. Previous research showed that affected individuals experienced distal muscle weakness starting in adolescence, along with mild facial muscle weakness, slightly elevated or normal serum creatine kinase (CK) levels, and the presence of a few rimmed vacuoles in muscle fibers or minimal chronic myopathic damage. Previously reported patients in this category exhibited an early age of symptom onset and severe muscle weakness. In this study, we present a case of two sisters who share the same mutation locus but display distinct disease phenotypes. Methods A literature review was conducted on distal myopathies in patients with ADSSL1 mutations, alongside a retrospective analysis of disease severity variability among siblings with a homozygous missense variant of ADSSL1. Results The study focuses on two sisters with differing disease manifestations despite carrying the same genetic mutation. The older sister showed lower ability in running and jumping compared to her peers at age 7 and experienced notable muscle weakness and atrophy by age 27, whereas the younger sister remained free of symptoms at age 30. Conclusion These findings suggest that mutations at the same locus can result in varying disease outcomes, emphasizing the complexity of predicting disease progression based solely on genetic mutations.https://doi.org/10.1002/mgg3.70041ADSSL1different manifestationdistal myopathyhomozygous variants
spellingShingle Hui Wang
Ting Zhang
Yanming Xu
Wenhui Fan
Variability in Disease Severity in Siblings With Homozygous Missense Variant of ADSSL1: Clinical Genetic Study and Review of Literatures
Molecular Genetics & Genomic Medicine
ADSSL1
different manifestation
distal myopathy
homozygous variants
title Variability in Disease Severity in Siblings With Homozygous Missense Variant of ADSSL1: Clinical Genetic Study and Review of Literatures
title_full Variability in Disease Severity in Siblings With Homozygous Missense Variant of ADSSL1: Clinical Genetic Study and Review of Literatures
title_fullStr Variability in Disease Severity in Siblings With Homozygous Missense Variant of ADSSL1: Clinical Genetic Study and Review of Literatures
title_full_unstemmed Variability in Disease Severity in Siblings With Homozygous Missense Variant of ADSSL1: Clinical Genetic Study and Review of Literatures
title_short Variability in Disease Severity in Siblings With Homozygous Missense Variant of ADSSL1: Clinical Genetic Study and Review of Literatures
title_sort variability in disease severity in siblings with homozygous missense variant of adssl1 clinical genetic study and review of literatures
topic ADSSL1
different manifestation
distal myopathy
homozygous variants
url https://doi.org/10.1002/mgg3.70041
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AT yanmingxu variabilityindiseaseseverityinsiblingswithhomozygousmissensevariantofadssl1clinicalgeneticstudyandreviewofliteratures
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