Document Detail

Genotype-phenotype study in an FSHD family with a proximal deletion encompassing p13E-11 and D4Z4.
MedLine Citation:
PMID:  17229919     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: In the majority of facioscapulohumeral muscular dystrophy (FSHD) cases, the molecular basis of the disease is due to loss of subtelomeric D4Z4 repeat units at 4q35. Occasionally, an apparent absence of the contracted D4Z4 repeat is associated with FSHD. One explanation for this finding is a deletion in the region proximal to the D4Z4 repeat array that encompasses the p13E-11 (D4F104S1) probe-binding site used in the DNA diagnosis. The frequency of such proximally extended deletions is unknown, and to date, few patients have been described due to the difficulties in the molecular identification of such cases. METHODS: We describe a family (DUK 2531) in which a contracted D4Z4 allele and a large proximal deletion of approximately 75 kb are segregating to 11 individuals. This is the largest deletion identified to date. Family DUK 2531 was initially thought to have normal D4Z4 fragment size and therefore unlinked to the 4q35 region (FSHD1B). RESULTS: Further molecular analysis of DUK 2531 reveals the presence of 10 repeat units (33 kb). The extended deletion includes the probe p13E-11 and B31 binding sites, the inverted repeat D4S2463, and genes FRG2 and TUBB4Q. CONCLUSION: Despite the length of the proximal deletion in this family, the range and severity of the clinical manifestations are typical for the disorder. Because such deletions can lead to misinterpretation in the diagnostic setting, this suggests the need for additional diagnostic tests in facioscapulohumeral muscular dystrophy.
K L Deak; R J L F Lemmers; J M Stajich; R Klooster; R Tawil; R R Frants; M C Speer; S M van der Maarel; J R Gilbert
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-01-17
Journal Detail:
Title:  Neurology     Volume:  68     ISSN:  1526-632X     ISO Abbreviation:  Neurology     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-20     Completed Date:  2007-03-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0401060     Medline TA:  Neurology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  578-82     Citation Subset:  AIM; IM    
Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.
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MeSH Terms
Chromosome Aberrations
Chromosomes, Human, Pair 4 / genetics*
DNA Mutational Analysis
Gene Deletion*
Gene Dosage / genetics
Gene Frequency / genetics
Genetic Predisposition to Disease / genetics*
Genetic Testing
Muscle Weakness / diagnosis,  genetics,  physiopathology
Muscle, Skeletal / pathology,  physiopathology
Muscular Dystrophy, Facioscapulohumeral / diagnosis,  genetics*,  physiopathology*
Mutation / genetics*
Grant Support
Comment In:
Neurology. 2007 Feb 20;68(8):544-5   [PMID:  17310022 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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