Naslov
Clinical Variability and Molecular Diagnosis in a Four-generation family with X-linked Emery-Dreifuss muscular Dystrophy

Autori
Canki-Klain, Nina ; Recan, Dominique ; Miličić, Davor ; Llense, Stephane ; Leturcq, France ; Deburgrave, Nathalie ; Kaplan, Jean-Claude ; Debevec, Marija ; Zurak, Niko

Izvornik
Croatian Medical Journal (0353-9504) 41 (2000), 4; 389-395

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
carrier state; frameshift mutation; heart conduction system; muscular dystrophy; Emery-Dreifuss; mutation; frameshift; mutational analysis; DNA; phenotype

Sažetak
Aim. To describe the clinical variability of X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) with cardiac involvement in a four-generation family with a novel mutation in STA gene. Methods. Clinical data were provided for 4 affected males and female carrier. The Western blot analysis of emerin was performed on lymphoblastoid cell lines and followed by sequencing of the emerin gene. Result. A thyamine insertion at nucleotide 417 in exon 2, resulting in a frameshift with a premature stop codon at position 62 and absence of functional protein, was found in one of three avaliable patients. In ten-year-old proband's dizygotic twin-nephews the intermittent first-degree A-V block, atrial and ventricular ectopy, atrial runs, and exit sinus block were found, although the echocardiographic findings were normal. One of the twins also had short episodes of atrial fibrillation, idioventricular rhythm, and junctional rhythm. Conclusion Cardiac abnormalities in the proband's ten-year-old dizygotic twins without evident clinical features suggestive of EDMD were remarkable in contrast to the oldest patient in the family, who lived to the age of 63 without pacemaker, and to the proband who had a very early onset of muscular wasting and weaknes, and a pacemaker implantation at the age of 27. This striking intra-familial variability in cardiac involvement associated with specific null mutation (417 ins T)has practical early diagnostic and possibly preventive implications. It als points at genetic and environmental factors as cause of clinical features in X-EDMD.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA