TY - JOUR
T1 - A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome
AU - Barrientos, Antoni
AU - Volpini, Víctor
AU - Casademont, Jordi
AU - Genís, David
AU - Manzanares, Josep Maria
AU - Ferrer, Isidre
AU - Corral, Jordi
AU - Cardellach, Francesc
AU - Urbano-Márquez, Alvaro
AU - Estivill, Xavier
AU - Nunes, Virginia
PY - 1996/4/1
Y1 - 1996/4/1
N2 - Wolfram syndrome is a progressive neurodegenerative disorder transmitted in an autosomal recessive mode. We report two Wolfram syndrome families harboring multiple deletions of mitochondrial DNA. The deletions reached percentages as high as 85-90% in affected tissues such as the central nervous system of one patient, while in other tissues from the same patient and from other members of the family, the percentages of deleted mitochondrial DNA genomes were only 1-10%. Recently, a Wolfram syndrome gene has been linked to markers on 4p16. In both families linkage between the disease locus and 4p16 markers gave a maximum multipoint lod score of 3.79 at θ = 0 (P < 0.03) with respect to D4S431. In these families, the syndrome was caused by mutations in this nucleus-encoded gene which deleteriously interacts with the mitochondrial genome. This is the first evidence of the implication of both genomes in a recessive disease.
AB - Wolfram syndrome is a progressive neurodegenerative disorder transmitted in an autosomal recessive mode. We report two Wolfram syndrome families harboring multiple deletions of mitochondrial DNA. The deletions reached percentages as high as 85-90% in affected tissues such as the central nervous system of one patient, while in other tissues from the same patient and from other members of the family, the percentages of deleted mitochondrial DNA genomes were only 1-10%. Recently, a Wolfram syndrome gene has been linked to markers on 4p16. In both families linkage between the disease locus and 4p16 markers gave a maximum multipoint lod score of 3.79 at θ = 0 (P < 0.03) with respect to D4S431. In these families, the syndrome was caused by mutations in this nucleus-encoded gene which deleteriously interacts with the mitochondrial genome. This is the first evidence of the implication of both genomes in a recessive disease.
KW - autosomal recessive inheritance
KW - DIDMOAD
KW - linkage
KW - neurodegenerative disease
KW - OXPHOS
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U2 - 10.1172/JCI118581
DO - 10.1172/JCI118581
M3 - Article
C2 - 8601620
AN - SCOPUS:13344260008
VL - 97
SP - 1570
EP - 1576
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 7
ER -