TY - JOUR
T1 - Complex multisystem phenotype associated with the mitochondrial DNA m.5522G>A mutation
AU - Nesti, Claudia
AU - Rubegni, Anna
AU - Tolomeo, Deborah
AU - Baldacci, Jacopo
AU - Cassandrini, Denise
AU - D’Amore, Francesca
AU - Santorelli, Filippo M.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Mitochondrial tRNAs are responsible for more than half of pathogenic point mutations in the mitochondrial genome (mtDNA). Different mutations give rise to widely differing phenotypes, ranging from isolated organ-specific diseases to multisystem conditions. Herein, we report a 40-year-old woman presenting with a complex multisystem phenotype including sensorineural hearing loss, retinopathy, severe dilated cardiomyopathy, non-insulin dependent diabetes mellitus, and renal failure. Sequence analysis of mtDNA identified the m.5522G>A mutation in MT-TW, the gene encoding mitochondrial tRNA for tryptophan. The heteroplasmic variant, thus far described once, was almost exclusively confined to skeletal muscle tissue, as shown by massive parallel sequencing and corroborated by an ad hoc designed PCR-based strategy. This patient, presenting a severe, multisystem involvement apparently sparing the brain, contributes to the genetic heterogeneity of mitochondrial diseases caused by mutations in mitochondrial tRNAs.
AB - Mitochondrial tRNAs are responsible for more than half of pathogenic point mutations in the mitochondrial genome (mtDNA). Different mutations give rise to widely differing phenotypes, ranging from isolated organ-specific diseases to multisystem conditions. Herein, we report a 40-year-old woman presenting with a complex multisystem phenotype including sensorineural hearing loss, retinopathy, severe dilated cardiomyopathy, non-insulin dependent diabetes mellitus, and renal failure. Sequence analysis of mtDNA identified the m.5522G>A mutation in MT-TW, the gene encoding mitochondrial tRNA for tryptophan. The heteroplasmic variant, thus far described once, was almost exclusively confined to skeletal muscle tissue, as shown by massive parallel sequencing and corroborated by an ad hoc designed PCR-based strategy. This patient, presenting a severe, multisystem involvement apparently sparing the brain, contributes to the genetic heterogeneity of mitochondrial diseases caused by mutations in mitochondrial tRNAs.
KW - Heteroplasmy
KW - Massive parallel sequencing
KW - mtDNA mutation
KW - Multisystem disorder
KW - tRNA
UR - http://www.scopus.com/inward/record.url?scp=85064218604&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064218604&partnerID=8YFLogxK
U2 - 10.1007/s10072-019-03864-w
DO - 10.1007/s10072-019-03864-w
M3 - Article
C2 - 30937556
AN - SCOPUS:85064218604
VL - 40
SP - 1705
EP - 1708
JO - Neurological Sciences
JF - Neurological Sciences
SN - 1590-1874
IS - 8
ER -