ABSTRACT
We sequenced all genes of mitochondrial tRNAs of a patient with chronic progressive external ophthalmoplegia with 5% ragged red fibres and 15% COX-negative fibres but without macrorearrangements of mitochondrial DNA (mtDNA). Direct sequencing showed a novel heteroplasmic G>A substitution in position 12316 of tRNA(Leu(CUN)) gene. This change destroys a highly conserved G-C base coupling in tRNA TpsiC branch. By RFLP analysis we could demonstrate different degrees of heteroplasmy in different patient's tissues. This alteration, absent in a population of 110 patients with different encephalomyopathies, can be considered pathogenic: it is the tenth tRNA(Leu(CUN)) pathogenic mutation described up to date.
Subject(s)
DNA, Mitochondrial/genetics , Mutation , Ophthalmoplegia, Chronic Progressive External/genetics , RNA, Transfer, Leu/genetics , DNA Mutational Analysis , Female , Humans , Middle Aged , Muscle, Skeletal/pathology , Ophthalmoplegia, Chronic Progressive External/pathologySubject(s)
Biopsy , CADASIL/diagnosis , Skin/ultrastructure , Tunica Media/ultrastructure , Adult , Aged , Arterioles/chemistry , Arterioles/ultrastructure , Brain/blood supply , CADASIL/genetics , CADASIL/pathology , Coloring Agents , DNA Mutational Analysis , Exons/genetics , Female , Humans , Male , Middle Aged , Organ Specificity , Receptor, Notch3 , Receptors, Notch/genetics , Sensitivity and Specificity , Skin/blood supply , Tunica Media/chemistrySubject(s)
Intellectual Disability/pathology , Myoclonic Cerebellar Dyssynergia/pathology , Pupil Disorders/pathology , Adult , Biopsy , Electromyography , Family , Fathers , Female , Humans , Intellectual Disability/genetics , Magnetic Resonance Imaging , Male , Middle Aged , Muscle, Skeletal/pathology , Myoclonic Cerebellar Dyssynergia/genetics , Parents , Pupil Disorders/geneticsABSTRACT
We report the case of a 41-year-old patient with bilateral hemorrhage of the thalamus, leading to death. Post-mortem examination showed acute myocarditis. Neuropathological study showed perivascular infiltrates in affected thalamic regions. Laboratory investigation failed to find any causal agent. We hypothesize an infective agent, affecting the heart and thalamus, as the cause of this syndrome. Diaschisis due to the strategic anatomical position of the thalamus may have been responsible for coma state and death.
