Novel and recurrent mutations in lamin A/C in patients with Emery-Dreifuss muscular dystrophy
| Autor: | Kimberly Q. McKinney, Takeshi Sasaki, Ann R. Salvino, Peter Heydemann, Oksana Suchowersky, Jerry R. Mendell, David A. Simpson, J. Edward Spence, Carol A. Crowe, Cheryl R. Greenberg, Basil T. Darras, Carla Grosmann, Frederick Shapiro, Robert W. Lanning, Elizabeth M. Cherniske, Charlotte A. Brown, Barbara R. Pober, Stasha Gominak |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Molecular Sequence Data Emerin Biology medicine.disease_cause Muscular Dystrophies LMNA Exon medicine Humans Missense mutation Amino Acid Sequence Muscular dystrophy Emery–Dreifuss muscular dystrophy Child Genetics (clinical) Genetics Mutation integumentary system Nuclear Proteins Middle Aged Lamin Type A medicine.disease Lamins Muscular Dystrophy Emery-Dreifuss Pedigree Child Preschool Female Lamin |
| Zdroj: | American Journal of Medical Genetics. 102:359-367 |
| ISSN: | 1096-8628 0148-7299 |
| DOI: | 10.1002/ajmg.1463 |
| Popis: | Emery-Dreifuss muscular dystrophy (EDMD) is characterized by slowly progressive muscle wasting and weakness; early contractures of the elbows, Achilles tendons, and spine; and cardiomyopathy associated with cardiac conduction defects. Clinically indistinguishable X-linked and autosomal forms of EDMD have been described. Mutations in the STA gene, encoding the nuclear envelope protein emerin, are responsible for X-linked EDMD, while mutations in the LMNA gene encoding lamins A and C by alternative splicing have been found in patients with autosomal dominant, autosomal recessive, and sporadic forms of EDMD. We report mutations in LMNA found in four familial and seven sporadic cases of EDMD, including seven novel mutations. Nine missense mutations and two small in-frame deletions were detected distributed throughout the gene. Most mutations (7/11) were detected within the LMNA exons encoding the central rod domain common to both lamins A/C. All of these missense mutations alter residues in the lamin A/C proteins conserved throughout evolution, implying an essential structural and/or functional role of these residues. One severely affected patient possesed two mutations, one specific to lamin A that may modify the phenotype of this patient. Mutations in LMNA were frequently identified among patients with sporadic and familial forms of EDMD. Further studies are needed to identify the factors modifying disease phenotype among patients harboring mutations within lamin A/C and to determine the effect of various mutations on lamin A/C structure and function. |
| Databáze: | OpenAIRE |
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