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Tytuł pozycji:

Early onset collagen VI myopathies: Genetic and clinical correlations.

Tytuł :
Early onset collagen VI myopathies: Genetic and clinical correlations.
Autorzy :
Briñas L; Inserm, U582, Paris, France.
Richard P
Quijano-Roy S
Gartioux C
Ledeuil C
Lacène E
Makri S
Ferreiro A
Maugenre S
Topaloglu H
Haliloglu G
Pénisson-Besnier I
Jeannet PY
Merlini L
Navarro C
Toutain A
Chaigne D
Desguerre I
de Die-Smulders C
Dunand M
Echenne B
Eymard B
Kuntzer T
Maincent K
Mayer M
Plessis G
Rivier F
Roelens F
Stojkovic T
Taratuto AL
Lubieniecki F
Monges S
Tranchant C
Viollet L
Romero NB
Estournet B
Guicheney P
Allamand V
Pokaż więcej
Źródło :
Annals of neurology [Ann Neurol] 2010 Oct; Vol. 68 (4), pp. 511-20.
Typ publikacji :
Journal Article; Research Support, Non-U.S. Gov't
Język :
English
Imprint Name(s) :
Publication: New York, NY : Wiley-Liss
Original Publication: Boston, Little, Brown.
MeSH Terms :
Muscular Diseases*/genetics
Muscular Diseases*/metabolism
Muscular Diseases*/pathology
Statistics as Topic*
Collagen Type VII/*genetics
Collagen Type VII/*metabolism
Mutation/*genetics
Adolescent ; Adult ; Cells, Cultured ; Child ; Child, Preschool ; Europe ; Female ; Fibroblasts/metabolism ; Genetic Testing/methods ; Glycine/genetics ; Humans ; Male ; Muscle, Skeletal/metabolism ; Phenotype ; Young Adult
Substance Nomenclature :
0 (Collagen Type VII)
TE7660XO1C (Glycine)
Entry Date(s) :
Date Created: 20101027 Date Completed: 20101112 Latest Revision: 20131121
Update Code :
20210210
DOI :
10.1002/ana.22087
PMID :
20976770
Czasopismo naukowe
Objective: Mutations in the genes encoding the extracellular matrix protein collagen VI (ColVI) cause a spectrum of disorders with variable inheritance including Ullrich congenital muscular dystrophy, Bethlem myopathy, and intermediate phenotypes. We extensively characterized, at the clinical, cellular, and molecular levels, 49 patients with onset in the first 2 years of life to investigate genotype-phenotype correlations.
Methods: Patients were classified into 3 groups: early-severe (18%), moderate-progressive (53%), and mild (29%). ColVI secretion was analyzed in patient-derived skin fibroblasts. Chain-specific transcript levels were quantified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and mutation identification was performed by sequencing of complementary DNA.
Results: ColVI secretion was altered in all fibroblast cultures studied. We identified 56 mutations, mostly novel and private. Dominant de novo mutations were detected in 61% of the cases. Importantly, mutations causing premature termination codons (PTCs) or in-frame insertions strikingly destabilized the corresponding transcripts. Homozygous PTC-causing mutations in the triple helix domains led to the most severe phenotypes (ambulation never achieved), whereas dominant de novo in-frame exon skipping and glycine missense mutations were identified in patients of the moderate-progressive group (loss of ambulation).
Interpretation: This work emphasizes that the diagnosis of early onset ColVI myopathies is arduous and time-consuming, and demonstrates that quantitative RT-PCR is a helpful tool for the identification of some mutation-bearing genes. Moreover, the clinical classification proposed allowed genotype-phenotype relationships to be explored, and may be useful in the design of future clinical trials.

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