Screening for PRX mutations in a large Chinese Charcot-Marie-Tooth disease cohort and literature review
BackgroundPeriaxins (encoded by PRX) play an important role in the stabilization of peripheral nerve myelin. Mutations in PRX can lead to Charcot-Marie-Tooth disease type 4F (CMT4F).MethodsIn this study, we screened for PRX mutations using next-generation sequencing and whole-exome sequencing in a l...
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1148044/full |
| _version_ | 1827909421273972736 |
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| author | Xinran Ma Xinran Ma Xinran Ma Xiaoxuan Liu Xiaoxuan Liu Xiaoxuan Liu Xiaohui Duan Dongsheng Fan Dongsheng Fan Dongsheng Fan |
| author_facet | Xinran Ma Xinran Ma Xinran Ma Xiaoxuan Liu Xiaoxuan Liu Xiaoxuan Liu Xiaohui Duan Dongsheng Fan Dongsheng Fan Dongsheng Fan |
| author_sort | Xinran Ma |
| collection | DOAJ |
| description | BackgroundPeriaxins (encoded by PRX) play an important role in the stabilization of peripheral nerve myelin. Mutations in PRX can lead to Charcot-Marie-Tooth disease type 4F (CMT4F).MethodsIn this study, we screened for PRX mutations using next-generation sequencing and whole-exome sequencing in a large Chinese CMT cohort consisting of 465 unrelated index patients and 650 healthy controls. Sanger sequencing was used for the validation of all identified variants. We also reviewed all previously reported PRX-related CMT cases and summarized the clinical manifestations and genetic features of PRX-related CMTs.ResultsThe hit rate for biallelic PRX variants in our cohort of Chinese CMT patients was 0.43% (2/465). One patient carried a previously unreported splice-site mutation (c.25_27 + 9del) compound heterozygous with a known nonsense variant. Compiling data on CMT4F cases and PRX variants from the medical literature confirmed that early-onset (95.2%), distal amyotrophy or weakness (94.0%), feet deformity (75.0%), sensory impairment or sensory ataxia (65.5%), delayed motor milestones (60.7%), and spinal deformity (59.5%) are typical features for CMT4F. Less frequent features were auditory impairments, respiratory symptoms, late onset, dysarthria or hoarseness, ophthalmic problems, and central nervous system involvement. The two cases with biallelic missense mutations have later onset age than those with nonsense or frameshift mutations. We did not note clear correlations between the type and site of mutations and clinical severity or distinct constellations of symptoms.ConclusionConsistent with observations in other countries and ethnic groups, PRX-related CMT is rare in China. The clinical spectrum is wider than previously anticipated. |
| first_indexed | 2024-03-13T01:36:49Z |
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| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-03-13T01:36:49Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-5c1ec0975c8b43db956b660352b10bd92023-07-04T04:45:48ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-07-011410.3389/fneur.2023.11480441148044Screening for PRX mutations in a large Chinese Charcot-Marie-Tooth disease cohort and literature reviewXinran Ma0Xinran Ma1Xinran Ma2Xiaoxuan Liu3Xiaoxuan Liu4Xiaoxuan Liu5Xiaohui Duan6Dongsheng Fan7Dongsheng Fan8Dongsheng Fan9Department of Neurology, Peking University Third Hospital, Beijing, ChinaKey Laboratory for Neuroscience, National Health Commission/Ministry of Education, Peking University, Beijing, ChinaBeijing Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, ChinaDepartment of Neurology, Peking University Third Hospital, Beijing, ChinaKey Laboratory for Neuroscience, National Health Commission/Ministry of Education, Peking University, Beijing, ChinaBeijing Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, ChinaDepartment of Neurology, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Neurology, Peking University Third Hospital, Beijing, ChinaKey Laboratory for Neuroscience, National Health Commission/Ministry of Education, Peking University, Beijing, ChinaBeijing Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, ChinaBackgroundPeriaxins (encoded by PRX) play an important role in the stabilization of peripheral nerve myelin. Mutations in PRX can lead to Charcot-Marie-Tooth disease type 4F (CMT4F).MethodsIn this study, we screened for PRX mutations using next-generation sequencing and whole-exome sequencing in a large Chinese CMT cohort consisting of 465 unrelated index patients and 650 healthy controls. Sanger sequencing was used for the validation of all identified variants. We also reviewed all previously reported PRX-related CMT cases and summarized the clinical manifestations and genetic features of PRX-related CMTs.ResultsThe hit rate for biallelic PRX variants in our cohort of Chinese CMT patients was 0.43% (2/465). One patient carried a previously unreported splice-site mutation (c.25_27 + 9del) compound heterozygous with a known nonsense variant. Compiling data on CMT4F cases and PRX variants from the medical literature confirmed that early-onset (95.2%), distal amyotrophy or weakness (94.0%), feet deformity (75.0%), sensory impairment or sensory ataxia (65.5%), delayed motor milestones (60.7%), and spinal deformity (59.5%) are typical features for CMT4F. Less frequent features were auditory impairments, respiratory symptoms, late onset, dysarthria or hoarseness, ophthalmic problems, and central nervous system involvement. The two cases with biallelic missense mutations have later onset age than those with nonsense or frameshift mutations. We did not note clear correlations between the type and site of mutations and clinical severity or distinct constellations of symptoms.ConclusionConsistent with observations in other countries and ethnic groups, PRX-related CMT is rare in China. The clinical spectrum is wider than previously anticipated.https://www.frontiersin.org/articles/10.3389/fneur.2023.1148044/fullCharcot-Marie-Tooth diseaseperiaxinmutationwhole-exome sequencingnext-generation sequencing |
| spellingShingle | Xinran Ma Xinran Ma Xinran Ma Xiaoxuan Liu Xiaoxuan Liu Xiaoxuan Liu Xiaohui Duan Dongsheng Fan Dongsheng Fan Dongsheng Fan Screening for PRX mutations in a large Chinese Charcot-Marie-Tooth disease cohort and literature review Frontiers in Neurology Charcot-Marie-Tooth disease periaxin mutation whole-exome sequencing next-generation sequencing |
| title | Screening for PRX mutations in a large Chinese Charcot-Marie-Tooth disease cohort and literature review |
| title_full | Screening for PRX mutations in a large Chinese Charcot-Marie-Tooth disease cohort and literature review |
| title_fullStr | Screening for PRX mutations in a large Chinese Charcot-Marie-Tooth disease cohort and literature review |
| title_full_unstemmed | Screening for PRX mutations in a large Chinese Charcot-Marie-Tooth disease cohort and literature review |
| title_short | Screening for PRX mutations in a large Chinese Charcot-Marie-Tooth disease cohort and literature review |
| title_sort | screening for prx mutations in a large chinese charcot marie tooth disease cohort and literature review |
| topic | Charcot-Marie-Tooth disease periaxin mutation whole-exome sequencing next-generation sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1148044/full |
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