TY - JOUR
T1 - Clinical and molecular features of adPEO due to mutations in the Twinkle gene
AU - Lewis, Sharon
AU - Hutchison, Wendy
AU - Thyagarajan, Dominic
AU - Dahl, Hans Henrik M.
PY - 2002/9/15
Y1 - 2002/9/15
N2 - We have analyzed Twinkle, the causative gene for autosomal dominant progressive external ophthalmoplegia (adPEO) on chromosome 10, in 11 Australian autosomal dominant progressive external ophthalmoplegia families of Caucasian origin, and investigated whether there are distinct molecular and clinical features associated with mutations in this gene. We found two new mutations in Twinkle, in 3 of the 11 pedigrees examined. One resides in the linker region of this gene while the other is in the primase domain. Both regions are highly conserved between species. Multiple deletions in the mtDNA from muscle are not always prominent and there are significant variations in the clinical presentation within and between families with mutations in the Twinkle gene. Therefore, genotype/phenotype predictions are difficult. No mutations were found in adenine nucleotide translocator 1 (ANT1), another known adPEO causative gene, in four of the seven remaining families investigated. Thus, Twinkle appears to be the most common gene associated with adPEO in Australian families.
AB - We have analyzed Twinkle, the causative gene for autosomal dominant progressive external ophthalmoplegia (adPEO) on chromosome 10, in 11 Australian autosomal dominant progressive external ophthalmoplegia families of Caucasian origin, and investigated whether there are distinct molecular and clinical features associated with mutations in this gene. We found two new mutations in Twinkle, in 3 of the 11 pedigrees examined. One resides in the linker region of this gene while the other is in the primase domain. Both regions are highly conserved between species. Multiple deletions in the mtDNA from muscle are not always prominent and there are significant variations in the clinical presentation within and between families with mutations in the Twinkle gene. Therefore, genotype/phenotype predictions are difficult. No mutations were found in adenine nucleotide translocator 1 (ANT1), another known adPEO causative gene, in four of the seven remaining families investigated. Thus, Twinkle appears to be the most common gene associated with adPEO in Australian families.
KW - adPEO
KW - Australian pedigrees
KW - Clinical variations
KW - Novel mutations
KW - Twinkle
UR - http://www.scopus.com/inward/record.url?scp=0037105957&partnerID=8YFLogxK
U2 - 10.1016/S0022-510X(02)00190-9
DO - 10.1016/S0022-510X(02)00190-9
M3 - Article
C2 - 12163192
AN - SCOPUS:0037105957
SN - 0022-510X
VL - 201
SP - 39
EP - 44
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 1-2
ER -