A female patient carrying a novel DMD mutation with non-random X-chromosome inactivation from a DMD family
Abstract Objective To analyze the clinical phenotype and genetic characteristics of a female proband carrying a novel mutation in the DMD gene with non-random X-chromosome inactivation in a large pedigree with pseudohypertrophic muscular dystrophy. Methods Clinical information of the female proband,...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | BMC Medical Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12920-024-01794-x |
| _version_ | 1797272875969806336 |
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| author | Ming-Xia Sun Miao Jing Ying Hua Jian-Biao Wang Sheng-Quan Wang Li-Lan Chen Liang Ju Yan-Shan Liu |
| author_facet | Ming-Xia Sun Miao Jing Ying Hua Jian-Biao Wang Sheng-Quan Wang Li-Lan Chen Liang Ju Yan-Shan Liu |
| author_sort | Ming-Xia Sun |
| collection | DOAJ |
| description | Abstract Objective To analyze the clinical phenotype and genetic characteristics of a female proband carrying a novel mutation in the DMD gene with non-random X-chromosome inactivation in a large pedigree with pseudohypertrophic muscular dystrophy. Methods Clinical information of the female proband, her monozygotic twin sister, and other family members were collected. Potential pathogenic variants were detected with Multiplex Ligation-dependent Probe Amplification (MLPA) and whole-exome sequencing (WES). Methylation-sensitive restriction enzyme (HhaI) was employed for X-chromosome inactivation analysis. Results The proband was a female over 5 years old, displayed clinical manifestations such as elevated creatine kinase (CK) levels and mild calf muscle hypertrophy. Her monozygotic twin sister exhibited normal CK levels and motor ability. Her uncle and cousin had a history of DMD. WES revealed that the proband carried a novel variant in the DMD (OMIM: 300,377) gene: NM_004006.3: c.3051_3053dup; NP_003997.2: p.Tyr1018*. In this pedigree, five out of six female members were carriers of this variant, while the cousin and uncle were hemizygous for this variant. X-chromosome inactivation analysis suggested non-random inactivation in the proband. Conclusion The c.3051_3053dup (p.Tyr1018*) variant in the DMD gene is considered to be the pathogenic variant significantly associated with the clinical phenotype of the proband, her cousin, and her uncle within this family. Integrating genetic testing with clinical phenotype assessment can be a valuable tool for physicians in the diagnosis of progressive muscular dystrophies, such as Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD). |
| first_indexed | 2024-03-07T14:35:34Z |
| format | Article |
| id | doaj.art-1458b56c694c43fc8e1bebe219551201 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-03-07T14:35:34Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-1458b56c694c43fc8e1bebe2195512012024-03-05T20:39:15ZengBMCBMC Medical Genomics1755-87942024-02-011711710.1186/s12920-024-01794-xA female patient carrying a novel DMD mutation with non-random X-chromosome inactivation from a DMD familyMing-Xia Sun0Miao Jing1Ying Hua2Jian-Biao Wang3Sheng-Quan Wang4Li-Lan Chen5Liang Ju6Yan-Shan Liu7Department of Neurology, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital)Department of Neurology, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital)Department of Neurology, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital)Department of Neurology, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital)Department of Neurology, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital)Department of Neurology, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital)Department of Cardiology, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital)Department of Pediatric Laboratory, Affiliated Children’s Hospital of Jiangnan University (Wuxi Children’s Hospital)Abstract Objective To analyze the clinical phenotype and genetic characteristics of a female proband carrying a novel mutation in the DMD gene with non-random X-chromosome inactivation in a large pedigree with pseudohypertrophic muscular dystrophy. Methods Clinical information of the female proband, her monozygotic twin sister, and other family members were collected. Potential pathogenic variants were detected with Multiplex Ligation-dependent Probe Amplification (MLPA) and whole-exome sequencing (WES). Methylation-sensitive restriction enzyme (HhaI) was employed for X-chromosome inactivation analysis. Results The proband was a female over 5 years old, displayed clinical manifestations such as elevated creatine kinase (CK) levels and mild calf muscle hypertrophy. Her monozygotic twin sister exhibited normal CK levels and motor ability. Her uncle and cousin had a history of DMD. WES revealed that the proband carried a novel variant in the DMD (OMIM: 300,377) gene: NM_004006.3: c.3051_3053dup; NP_003997.2: p.Tyr1018*. In this pedigree, five out of six female members were carriers of this variant, while the cousin and uncle were hemizygous for this variant. X-chromosome inactivation analysis suggested non-random inactivation in the proband. Conclusion The c.3051_3053dup (p.Tyr1018*) variant in the DMD gene is considered to be the pathogenic variant significantly associated with the clinical phenotype of the proband, her cousin, and her uncle within this family. Integrating genetic testing with clinical phenotype assessment can be a valuable tool for physicians in the diagnosis of progressive muscular dystrophies, such as Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD).https://doi.org/10.1186/s12920-024-01794-xDMDManifesting carrierNovel mutationX-chromosome inactivation |
| spellingShingle | Ming-Xia Sun Miao Jing Ying Hua Jian-Biao Wang Sheng-Quan Wang Li-Lan Chen Liang Ju Yan-Shan Liu A female patient carrying a novel DMD mutation with non-random X-chromosome inactivation from a DMD family BMC Medical Genomics DMD Manifesting carrier Novel mutation X-chromosome inactivation |
| title | A female patient carrying a novel DMD mutation with non-random X-chromosome inactivation from a DMD family |
| title_full | A female patient carrying a novel DMD mutation with non-random X-chromosome inactivation from a DMD family |
| title_fullStr | A female patient carrying a novel DMD mutation with non-random X-chromosome inactivation from a DMD family |
| title_full_unstemmed | A female patient carrying a novel DMD mutation with non-random X-chromosome inactivation from a DMD family |
| title_short | A female patient carrying a novel DMD mutation with non-random X-chromosome inactivation from a DMD family |
| title_sort | female patient carrying a novel dmd mutation with non random x chromosome inactivation from a dmd family |
| topic | DMD Manifesting carrier Novel mutation X-chromosome inactivation |
| url | https://doi.org/10.1186/s12920-024-01794-x |
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