KLHL40-Related Myopathy: A Systematic Review and Insight into a Follow-up Biomarker via a New Case Report
Background: Mutations in the <i>KLHL40</i> gene are a common cause of severe or even lethal nemaline myopathy. Some cases with mild forms have been described, although the cases are still anecdotal. The aim of this paper was to systematically review the cases described in the literature...
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MDPI AG
2024-02-01
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| Online Access: | https://www.mdpi.com/2073-4425/15/2/208 |
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| author | Bianca Buchignani Gemma Marinella Rosa Pasquariello Giada Sgherri Silvia Frosini Filippo Maria Santorelli Alessandro Orsini Roberta Battini Guja Astrea |
| author_facet | Bianca Buchignani Gemma Marinella Rosa Pasquariello Giada Sgherri Silvia Frosini Filippo Maria Santorelli Alessandro Orsini Roberta Battini Guja Astrea |
| author_sort | Bianca Buchignani |
| collection | DOAJ |
| description | Background: Mutations in the <i>KLHL40</i> gene are a common cause of severe or even lethal nemaline myopathy. Some cases with mild forms have been described, although the cases are still anecdotal. The aim of this paper was to systematically review the cases described in the literature and to describe a 12-year clinical and imaging follow-up in an Italian patient with KLHL40- related myopathy in order to suggest possible follow-up measurements. Methods: Having searched through three electronic databases (PubMed, Scopus, and EBSCO), 18 articles describing 65 patients with homozygous or compound heterozygous <i>KLHL40</i> mutations were selected. A patient with a <i>KLHL40</i> homozygous mutation (c.1582G>A/p.E528K) was added and clinical and genetic data were collected. Results: The most common mutation identified in our systematic review was the (c.1516A>C) followed by the (c.1582G>A). In our review, 60% percent of the patients died within the first 4 years of life. Clinical features were similar across the sample. Unfortunately, however, there is no record of the natural history data in the surviving patients. The 12-year follow-up of our patient revealed a slow improvement in her clinical course, identifying muscle MRI as the only possible marker of disease progression. Conclusions: Due to its clinical and genotype homogeneity, KLHL40-related myopathy may be a condition that would greatly benefit from the development of new gene therapies; muscle MRI could be a good biomarker to monitor disease progression. |
| first_indexed | 2024-03-07T22:31:18Z |
| format | Article |
| id | doaj.art-17ea6281808a49b9967ea9fbaabf54df |
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| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-07T22:31:18Z |
| publishDate | 2024-02-01 |
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| record_format | Article |
| series | Genes |
| spelling | doaj.art-17ea6281808a49b9967ea9fbaabf54df2024-02-23T15:17:50ZengMDPI AGGenes2073-44252024-02-0115220810.3390/genes15020208KLHL40-Related Myopathy: A Systematic Review and Insight into a Follow-up Biomarker via a New Case ReportBianca Buchignani0Gemma Marinella1Rosa Pasquariello2Giada Sgherri3Silvia Frosini4Filippo Maria Santorelli5Alessandro Orsini6Roberta Battini7Guja Astrea8Department of Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, ItalyDepartment of Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, ItalyDepartment of Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, ItalyDepartment of Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, ItalyDepartment of Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, ItalyMolecular Medicine and Neurogenetics Unit, IRCCS Stella Maris Foundation, 56128 Pisa, ItalyPediatric Neurology, Azienda Ospedaliera Universitaria Pisana, 56100 Pisa, ItalyDepartment of Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, ItalyDepartment of Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, ItalyBackground: Mutations in the <i>KLHL40</i> gene are a common cause of severe or even lethal nemaline myopathy. Some cases with mild forms have been described, although the cases are still anecdotal. The aim of this paper was to systematically review the cases described in the literature and to describe a 12-year clinical and imaging follow-up in an Italian patient with KLHL40- related myopathy in order to suggest possible follow-up measurements. Methods: Having searched through three electronic databases (PubMed, Scopus, and EBSCO), 18 articles describing 65 patients with homozygous or compound heterozygous <i>KLHL40</i> mutations were selected. A patient with a <i>KLHL40</i> homozygous mutation (c.1582G>A/p.E528K) was added and clinical and genetic data were collected. Results: The most common mutation identified in our systematic review was the (c.1516A>C) followed by the (c.1582G>A). In our review, 60% percent of the patients died within the first 4 years of life. Clinical features were similar across the sample. Unfortunately, however, there is no record of the natural history data in the surviving patients. The 12-year follow-up of our patient revealed a slow improvement in her clinical course, identifying muscle MRI as the only possible marker of disease progression. Conclusions: Due to its clinical and genotype homogeneity, KLHL40-related myopathy may be a condition that would greatly benefit from the development of new gene therapies; muscle MRI could be a good biomarker to monitor disease progression.https://www.mdpi.com/2073-4425/15/2/208congenital myopathy<i>KLHL40</i>nemaline myopathiesKLHL40-related myopathy |
| spellingShingle | Bianca Buchignani Gemma Marinella Rosa Pasquariello Giada Sgherri Silvia Frosini Filippo Maria Santorelli Alessandro Orsini Roberta Battini Guja Astrea KLHL40-Related Myopathy: A Systematic Review and Insight into a Follow-up Biomarker via a New Case Report Genes congenital myopathy <i>KLHL40</i> nemaline myopathies KLHL40-related myopathy |
| title | KLHL40-Related Myopathy: A Systematic Review and Insight into a Follow-up Biomarker via a New Case Report |
| title_full | KLHL40-Related Myopathy: A Systematic Review and Insight into a Follow-up Biomarker via a New Case Report |
| title_fullStr | KLHL40-Related Myopathy: A Systematic Review and Insight into a Follow-up Biomarker via a New Case Report |
| title_full_unstemmed | KLHL40-Related Myopathy: A Systematic Review and Insight into a Follow-up Biomarker via a New Case Report |
| title_short | KLHL40-Related Myopathy: A Systematic Review and Insight into a Follow-up Biomarker via a New Case Report |
| title_sort | klhl40 related myopathy a systematic review and insight into a follow up biomarker via a new case report |
| topic | congenital myopathy <i>KLHL40</i> nemaline myopathies KLHL40-related myopathy |
| url | https://www.mdpi.com/2073-4425/15/2/208 |
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