New Insights into Genotype-phenotype Correlations in Chinese Facioscapulohumeral Muscular Dystrophy: A Retrospective Analysis of 178 Patients
Background: Facioscapulohumeral muscular dystrophy (FSHD), a common autosomal dominant muscular disorder, is caused by contraction of the D4Z4 repeats on 4q35. The complicated genotype-phenotype correlation among different ethnic population remains a controversial subject. We aimed to refine this co...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2015-01-01
|
| Series: | Chinese Medical Journal |
| Subjects: | |
| Online Access: | http://www.cmj.org/article.asp?issn=0366-6999;year=2015;volume=128;issue=13;spage=1707;epage=1713;aulast=Lin |
| _version_ | 1818421744077111296 |
|---|---|
| author | Feng Lin Zhi-Qiang Wang Min-Ting Lin Shen-Xing Murong Ning Wang |
| author_facet | Feng Lin Zhi-Qiang Wang Min-Ting Lin Shen-Xing Murong Ning Wang |
| author_sort | Feng Lin |
| collection | DOAJ |
| description | Background: Facioscapulohumeral muscular dystrophy (FSHD), a common autosomal dominant muscular disorder, is caused by contraction of the D4Z4 repeats on 4q35. The complicated genotype-phenotype correlation among different ethnic population remains a controversial subject. We aimed to refine this correlation in order to provide new information for genetic counseling.
Methods: Here, a cohort of 136 Chinese families including 178 affected individuals and 137 unaffected members were investigated. Genetic analyses were performed using the p13E-11, 4qA and 4qB probes after pulsed field gel electrophoresis separation and southern blotting. A 10-grade FSHD clinical severity scale was adopted for clinical assessment. The genotype-phenotype correlation was established by linear regression analyses.
Results: We observed a roughly inversed correlation between the short EcoRI fragment size and age-corrected clinical severity score in 154 symptomatic patients (P < 0.05). Compared to male patients, a significant higher proportion of females in both asymptomatic carriers and severe patients showed larger variation in the size of short EcoRI fragment. A high incidence (19/42, 45.2%) of asymptomatic (or minimally affected) carriers was found in familial members.
Conclusions: Although the number of D4Z4 repeats is known as one of the critical influences on genotype-phenotype correlation, a majority of phenotypic spectrum was still incompatible with their heterozygous contraction of the D4Z4 repeat, especial in female cases. Our results suggest that there are multi-factors synergistically modulating the phenotypic expression. |
| first_indexed | 2024-12-14T13:15:13Z |
| format | Article |
| id | doaj.art-4cd7d6ae0ac34356886360b845d5fdb0 |
| institution | Directory Open Access Journal |
| issn | 0366-6999 |
| language | English |
| last_indexed | 2024-12-14T13:15:13Z |
| publishDate | 2015-01-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Chinese Medical Journal |
| spelling | doaj.art-4cd7d6ae0ac34356886360b845d5fdb02022-12-21T23:00:05ZengWolters KluwerChinese Medical Journal0366-69992015-01-01128131707171310.4103/0366-6999.159336New Insights into Genotype-phenotype Correlations in Chinese Facioscapulohumeral Muscular Dystrophy: A Retrospective Analysis of 178 PatientsFeng LinZhi-Qiang WangMin-Ting LinShen-Xing MurongNing WangBackground: Facioscapulohumeral muscular dystrophy (FSHD), a common autosomal dominant muscular disorder, is caused by contraction of the D4Z4 repeats on 4q35. The complicated genotype-phenotype correlation among different ethnic population remains a controversial subject. We aimed to refine this correlation in order to provide new information for genetic counseling. Methods: Here, a cohort of 136 Chinese families including 178 affected individuals and 137 unaffected members were investigated. Genetic analyses were performed using the p13E-11, 4qA and 4qB probes after pulsed field gel electrophoresis separation and southern blotting. A 10-grade FSHD clinical severity scale was adopted for clinical assessment. The genotype-phenotype correlation was established by linear regression analyses. Results: We observed a roughly inversed correlation between the short EcoRI fragment size and age-corrected clinical severity score in 154 symptomatic patients (P < 0.05). Compared to male patients, a significant higher proportion of females in both asymptomatic carriers and severe patients showed larger variation in the size of short EcoRI fragment. A high incidence (19/42, 45.2%) of asymptomatic (or minimally affected) carriers was found in familial members. Conclusions: Although the number of D4Z4 repeats is known as one of the critical influences on genotype-phenotype correlation, a majority of phenotypic spectrum was still incompatible with their heterozygous contraction of the D4Z4 repeat, especial in female cases. Our results suggest that there are multi-factors synergistically modulating the phenotypic expression.http://www.cmj.org/article.asp?issn=0366-6999;year=2015;volume=128;issue=13;spage=1707;epage=1713;aulast=LinAsymptomatic; Facio-scapulohumeral Muscular Dystrophy; Genetic Counseling; Phenotype |
| spellingShingle | Feng Lin Zhi-Qiang Wang Min-Ting Lin Shen-Xing Murong Ning Wang New Insights into Genotype-phenotype Correlations in Chinese Facioscapulohumeral Muscular Dystrophy: A Retrospective Analysis of 178 Patients Chinese Medical Journal Asymptomatic; Facio-scapulohumeral Muscular Dystrophy; Genetic Counseling; Phenotype |
| title | New Insights into Genotype-phenotype Correlations in Chinese Facioscapulohumeral Muscular Dystrophy: A Retrospective Analysis of 178 Patients |
| title_full | New Insights into Genotype-phenotype Correlations in Chinese Facioscapulohumeral Muscular Dystrophy: A Retrospective Analysis of 178 Patients |
| title_fullStr | New Insights into Genotype-phenotype Correlations in Chinese Facioscapulohumeral Muscular Dystrophy: A Retrospective Analysis of 178 Patients |
| title_full_unstemmed | New Insights into Genotype-phenotype Correlations in Chinese Facioscapulohumeral Muscular Dystrophy: A Retrospective Analysis of 178 Patients |
| title_short | New Insights into Genotype-phenotype Correlations in Chinese Facioscapulohumeral Muscular Dystrophy: A Retrospective Analysis of 178 Patients |
| title_sort | new insights into genotype phenotype correlations in chinese facioscapulohumeral muscular dystrophy a retrospective analysis of 178 patients |
| topic | Asymptomatic; Facio-scapulohumeral Muscular Dystrophy; Genetic Counseling; Phenotype |
| url | http://www.cmj.org/article.asp?issn=0366-6999;year=2015;volume=128;issue=13;spage=1707;epage=1713;aulast=Lin |
| work_keys_str_mv | AT fenglin newinsightsintogenotypephenotypecorrelationsinchinesefacioscapulohumeralmusculardystrophyaretrospectiveanalysisof178patients AT zhiqiangwang newinsightsintogenotypephenotypecorrelationsinchinesefacioscapulohumeralmusculardystrophyaretrospectiveanalysisof178patients AT mintinglin newinsightsintogenotypephenotypecorrelationsinchinesefacioscapulohumeralmusculardystrophyaretrospectiveanalysisof178patients AT shenxingmurong newinsightsintogenotypephenotypecorrelationsinchinesefacioscapulohumeralmusculardystrophyaretrospectiveanalysisof178patients AT ningwang newinsightsintogenotypephenotypecorrelationsinchinesefacioscapulohumeralmusculardystrophyaretrospectiveanalysisof178patients |