Facioscapulohumeral muscular dystrophy. Phenotype-genotype correlation in patients with borderline D4Z4 repeat numbers

Facioscapulohumeral muscular dystrophy. Phenotype-genotype correlation in patients with borderline D4Z4 repeat numbers

Facioscapulohumeral muscular dystrophy (FSHD) is associated with a decreased number of D4Z4 repeats on chromosome 4q35. Diagnostic difficulties arise from atypical clinical presentations and from an overlap in D4Z4 numbers between controls and FSHD individuals. Thus, a molecular genetic test result...

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Bibliographic Details
Published in:Journal of neurology Vol. 250; no. 8; pp. 932 - 937
Main Authors: Butz, Miriam, Koch, Manuela C, Müller-Felber, Wolfgang, Lemmers, Richards J L F, van der Maarel, Silvère M, Schreiber, Herbert
Format: Journal Article
Language:English
Published: Germany Springer Nature B.V 01-08-2003
Subjects:
Adolescent
Adult
Age of Onset
Aged
Chromosome Mapping
Chromosomes, Human, Pair 4
Female
Genotype
Humans
Male
Middle Aged
Molecular Biology - methods
Muscular Dystrophy, Facioscapulohumeral - classification
Muscular Dystrophy, Facioscapulohumeral - genetics
Phenotype
Repetitive Sequences, Nucleic Acid - genetics
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Summary:Facioscapulohumeral muscular dystrophy (FSHD) is associated with a decreased number of D4Z4 repeats on chromosome 4q35. Diagnostic difficulties arise from atypical clinical presentations and from an overlap in D4Z4 numbers between controls and FSHD individuals. Thus, a molecular genetic test result with a borderline D4Z4 number has its limitations for the clinician wanting to differentiate between the diagnosis of FSHD and a myopathy presenting with FSHD-like symptoms.To investigate this problem in more detail we conducted a systematic study of 39 unrelated FSHD patients with borderline D4Z4 repeat numbers and 102 healthy controls. Our aim was threefold: [1] to define the molecular diagnostic cut-off point between FSHD cases and the control population, [2] to describe the myopathic spectrum in patients with borderline D4Z4 repeat numbers and [3] to look for correlations between D4Z4 number and clinical severity. The results indicate that there is no definite D4Z4 diagnostic cut-off point separating FSHD, FSHD-like myopathies and controls. A broad myopathic spectrum with four phenotypes (typical FSHD, facial-sparing FSHD, FSHD with atypical features, non-FSHD muscle disease) was found in the borderline region. The expected correlation of D4Z4 repeat number and clinical severity was not found. Therefore the molecular test is of limited help to differentiate FSHD from FSHDlike muscle disorders when the D4Z4 number is n = >or= 8.
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ISSN:0340-5354
1432-1459
DOI:10.1007/s00415-003-1116-y