50 research outputs found
Mitochondrial disease in Southwestern Finland. Population-based molecular genetic and clinical studies
Mitochondria are present in all eukaryotic cells. They enable these cells utilize oxygen
in the production of adenosine triphosphate in the oxidative phosphorylation system,
the mitochondrial respiratory chain. The concept ‘mitochondrial disease’ conventionally
refers to disorders of the respiratory chain that lead to oxidative phosphorylation defect.
Mitochondrial disease in humans can present at any age, and practically in any organ
system. Mitochondrial disease can be inherited in maternal, autosomal dominant,
autosomal recessive, or X-chromosomal fashion. One of the most common molecular
etiologies of mitochondrial disease in population is the m.3243A>G mutation in the
MT-TL1 gene, encoding mitochondrial tRNALeu(UUR). Clinical evaluation of patients
with m.3243A>G has revealed various typical clinical features, such as stroke-like
episodes, diabetes mellitus and sensorineural hearing loss. The prevalence and clinical
characteristics of mitochondrial disease in population are not well known. This
thesis consists of a series of studies, in which the prevalence and characteristics of
mitochondrial disease in the adult population of Southwestern Finland were assessed.
Mitochondrial haplogroup Uk was associated with increased risk of occipital ischemic
stroke among young women. Large-scale mitochondrial DNA deletions and mutations
of the POLG1 gene were the most common molecular etiologies of progressive external
ophthalmoplegia. Around 1% of diabetes mellitus emerging between the ages 18 – 45
years was associated with the m.3243A>G mutation. Moreover, among these young
diabetic patients, mitochondrial haplogroup U was associated with maternal family
history of diabetes. These studies demonstrate the usefulness of carefully planned
molecular epidemiological investigations in the study of mitochondrial disorders.Siirretty Doriast
Erikoislääkärikoulutuksen koejakso - muutakin kuin hyväksytty tai hylätty
Erikoislääkärikoulutuksen koejakson rakenne, tarkoitus ja toteuttamistapa ovat edelleen monelle koulutukseen hakevalle lääkärille ja erikoistujien arviointiin osallistuvalle erikoislääkärille epäselviä
Erikoislääkärikoulutuksen koejakso - muutakin kuin hyväksytty tai hylätty
Erikoislääkärikoulutuksen koejakson rakenne, tarkoitus ja toteuttamistapa ovat edelleen monelle koulutukseen hakevalle lääkärille ja erikoistujien arviointiin osallistuvalle erikoislääkärille epäselviä
Perheessä Parkinson - omaisen kuormitus sairauden eri vaiheissa
publishedVersionNon peer reviewe
Deep brain stimulation for monogenic Parkinson's disease : a systematic review
Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) patients with motor fluctuations and dyskinesias. The key DBS efficacy studies were performed in PD patients with unknown genotypes; however, given the estimated monogenic mutation prevalence of approximately 5-10%, most commonly LRRK2, PRKN, PINK1 and SNCA, and risk-increasing genetic factors such as GBA, proper characterization is becoming increasingly relevant. We performed a systematic review of 46 studies that reported DBS effects in 221 genetic PD patients. The results suggest that monogenic PD patients have variable DBS benefit depending on the mutated gene. Outcome appears excellent in patients with the most common LRRK2 mutation, p.G2019S, and good in patients with PRKN mutations but poor in patients with the more rare LRRK2 p.R1441G mutation. The overall benefit of DBS in SNCA, GBA and LRRK2 p.T2031S mutations may be compromised due to rapid progression of cognitive and neuropsychiatric symptoms. In the presence of other mutations, the motor changes in DBS-treated monogenic PD patients appear comparable to those of the general PD population.Peer reviewe
The m.7510T > C mutation: Hearing impairment and a complex neurologic phenotype
Objectives: Mutations in mitochondrial DNA cause a variety of clinical phenotypes ranging from a mild hearing impairment (HI) to severe encephalomyopathy. The MT-TS1 gene is a hotspot for mutations causing HI. The m.7510T>C mutation in MT-TS1 has been previously associated with non-syndromic HI in four families from different ethnic backgrounds.Materials and Methods: We describe the clinical, genetic, and histopathological findings in a Finnish family with the heteroplasmic m.7510T>C mutation in mitochondrial DNA.ResultsThe family proband presented with a progressive mitochondrial disease phenotype including migraine, epilepsy, mild ataxia, and cognitive impairment in addition to HI. One young adult presented with HI only. Other family members had a mild phenotype comprising ataxia and tremor in addition to HI. Mutation heteroplasmy was 90% in the blood of maternal grandmother and 99% in the muscle and blood of the three other family members. Muscle histology was consistent with mitochondrial myopathy in three family members. The mitochondrial haplogroup of the family was a different branch of the haplogroup H than in the previous reports of this mutation.Conclusion: Our results suggest that, in addition to sensorineural HI, the m.7510T>C mutation is associated with a spectrum of mitochondrial disease clinical features including migraine, epilepsy, cognitive impairment, ataxia, and tremor, and with evidence of mitochondrial myopathy
Deep brain stimulation for monogenic Parkinson’s disease: a systematic review
Deep brain stimulation (DBS) is an effective treatment for Parkinson’s disease (PD) patients with motor fluctuations and dyskinesias. The key DBS efficacy studies were performed in PD patients with unknown genotypes; however, given the estimated monogenic mutation prevalence of approximately 5–10%, most commonly LRRK2, PRKN, PINK1 and SNCA, and risk-increasing genetic factors such as GBA, proper characterization is becoming increasingly relevant. We performed a systematic review of 46 studies that reported DBS effects in 221 genetic PD patients. The results suggest that monogenic PD patients have variable DBS benefit depending on the mutated gene. Outcome appears excellent in patients with the most common LRRK2 mutation, p.G2019S, and good in patients with PRKN mutations but poor in patients with the more rare LRRK2 p.R1441G mutation. The overall benefit of DBS in SNCA, GBA and LRRK2 p.T2031S mutations may be compromised due to rapid progression of cognitive and neuropsychiatric symptoms. In the presence of other mutations, the motor changes in DBS-treated monogenic PD patients appear comparable to those of the general PD population.</p