Narrowing in on the causative defect of an intriguing X-linked myopathy with excessive autophagy.
Neurology
; 59(4): 596-601, 2002 Aug 27.
Article
em En
| MEDLINE
| ID: mdl-12196656
ABSTRACT
BACKGROUND:
X-Linked myopathy with excessive autophagy (XMEA) is a childhood-onset slowly progressive disease of skeletal muscle with no cardiac, nervous system, or other organ involvement. Pathology is distinctive membrane-bound autophagic vacuoles, multifold reduplication of the basement membrane, and intense deposition of membrane attack complex and calcium at the myofiber surface. XMEA has been linked to the most telomeric 10.5 cM of Xq28. The authors now report identification of new families, refinement of the locus, mapping of genes to the region, and screening of candidate genes for mutations. METHODS ANDRESULTS:
Seven new families were ascertained, including an American family with XMEA. Using 11 new microsatellite genetic markers, the authors fine-mapped a recombination in this family and a common ancestral haplotype in two French families, which localized the gene in a 4.37-Mb region. Sequence data were assembled from public and private databases and a near-continuous sequence derived for the entire region. With this sequence, a gene map of 82 genes and 28 expressed sequence tag clusters was constructed; to date, 12 candidate genes have been screened for mutations.CONCLUSIONS:
This study doubles the number of reported families with XMEA and more firmly establishes its distinctive clinicopathologic features. It also advances the search for the XMEA causative defect by reducing the disease locus to approximately half its previous size, assembling an almost complete sequence of the refined region, identifying all known genes in this sequence, and excluding the presence of mutations in 10% of these genes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Cromossomo X
/
Mapeamento Físico do Cromossomo
/
Ligação Genética
/
Doenças Musculares
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adolescent
/
Child
/
Humans
/
Male
País/Região como assunto:
America do norte
/
Europa
Idioma:
En
Revista:
Neurology
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Canadá