HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Orrell, R. W. Articles by Figlewicz, D. A. Search for Related Content PubMed PubMed Citation Articles by Orrell, R. W. Articles by Figlewicz, D. A.

Definitive molecular diagnosis of facioscapulohumeral dystrophy

From the Department of Neurology (Drs. Orrell, Tawil, Forrester, and Figlewicz), University of Rochester, NY; and the Department of Neurology (Drs. Kissel and Mendell), Ohio State University, Columbus, OH.

Address correspondence and reprint requests to Dr. Denise A. Figlewicz, Department of Neurology, Box 673, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642.

OBJECTIVE: To establish the usefulness of a molecular diagnostic protocol for the autosomal dominant disease facioscapulohumeral dystrophy (FSHD).

BACKGROUND: The genetic defect underlying the majority of cases is a deletion on chromosome 4q35 that is not associated with the coding sequence of any known gene. Molecular diagnosis of FSHD involves the visualization of this deletion as a "small" EcoRI restriction fragment. However, molecular diagnostics are complicated because of the homology of the telomeric regions of chromosomes 4q and 10q; the homologous 10q26 EcoRI fragments are also detected, and can fall into the size range considered to be diagnostic for FSHD. It is therefore important to distinguish the 4q35 and 10q26 EcoRI fragments, taking advantage of the presence of additional restriction sites (BlnI) in the alleles of chromosome 10q origin.

METHODS: Paired digests of genomic DNA (EcoRI only and EcoRI/BlnI double digest), followed by pulsed field gel electrophoresis (PFGE), were used to establish the molecular diagnosis of FSHD in 82 unrelated index cases (46 familial, 24 proven sporadic with de novo mutations, and 12 with uncertain family history).

RESULTS: In all cases fulfilling FSHD diagnostic criteria, a 4q35 EcoRI allele size of 38 kb was present. The smallest 4q35 EcoRI allele in 205 normal control subjects was 41 kb. EcoRI alleles 38 kb of chromosome 10q26 origin were present in 11.2% of this control group. In problematic cases, it was possible to resolve the diagnostic question.

CONCLUSIONS: The combination of double digestion with EcoRI and BlnI followed by PFGE is the most reliable molecular protocol for distinguishing patients with FSHD.

This article has been cited by other articles:

				S. Pandya, W. M King, and R. Tawil Facioscapulohumeral Dystrophy Physical Therapy, January 1, 2008; 88(1): 105 - 113. [Abstract] [Full Text] [PDF]

				L. D. Hobson-Webb Facioscapulohumeral Muscular Dystrophy Can Be a Cause of Isolated Childhood Cognitive Dysfunction J Child Neurol, March 1, 2006; 21(3): 252 - 253. [Abstract] [PDF]

				A J van der Kooi, M C Visser, N Rosenberg, R van den Berg-Vos, J H J Wokke, E Bakker, and M de Visser Extension of the clinical range of facioscapulohumeral dystrophy: report of six cases J. Neurol. Neurosurg. Psychiatry, July 1, 2000; 69(1): 114 - 116. [Abstract] [Full Text] [PDF]

				K. J. Felice, W. A. North, S. A. Moore, and K. D. Mathews FSH dystrophy 4q35 deletion in patients presenting with facial-sparing scapular myopathy Neurology, May 23, 2000; 54(10): 1927 - 1931. [Abstract] [Full Text] [PDF]