MOLECULAR DIAGNOSIS OF DYSTROPHINOPATHIES USING A MULTI-TECHNIQUE ANALYSIS ALGORITHM?

LEONELA N LUCE; OTTAVIANI DANIELA; FERRER MARCELA; , SZIJAN IRENE; COTIGNOLA JAVIER; FLORENCIA GILIBERTO,

MUSCLE & NERVE

JOHN WILEY & SONS INC

Lugar: New York; Año: 2014

0148-639X

ABSTRACT: Introduction: Dystrophinopathies are X-linkedrecessive neuromuscular diseases caused by mutations in thedystrophin gene. In this study we aimed to detect mutationswithin the dystrophin gene in DMD patients, to determine thecarrier status of women, and to perform a prenatal diagnosis.Methods: We analyzed 17 individuals from 2 unrelated familieswith a history of DMD. We used multiplex PCR, multiplexligation-dependent probe amplification (MLPA), and shorttandem-repeat (STR) segregation analysis to accurately detectand characterize the mutations and to identify the at-risk haplotype.Results: The selected methodology allowed for characterizationof 2 single-exon out-of-frame deletions in affectedpatients. Nine of 13 women and a fetus were excluded frombeing carriers. Three recombination events were found and suggestedthat germline mosaicism had occurred in both families.Conclusions: This methodology proved to be efficient for characterizingthe disease-causing mutation in affected individualsand for assessing the carrier status in healthy relatives. Thesefindings helped inform precise genetic counseling and contributedto characterization of the disease in the Argentinepopulation.