| 1. |
- Björkman, Kristoffer, et al.
(författare)
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Genotype-phenotype correlations in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1
- 2014
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Ingår i: Euromit 2014, 15-19 juni, Tampere, Finland.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To study genotype-phenotype correlations in genes encoding complex I electron input module subunits. Materials and methods: We studied five patients with isolated complex I deficiency, three with NDUFS1 mutations and two with NDUFV1 mutations. A literature review of all reported cases of mutations in the affected genes was performed. Results: The literature review revealed pathological mutations in NDUFS1 for 18 patients in 17 families and correspondingly in NDUFV1 for 26 patients in 19 families. Unpublished clinical data for our five patients were added. Our study showed quite variable clinical courses; death before two years of age was seen in 41% of patients while 18% were alive at seven years. There was a significant difference between the NDUFS1 and NDUFV1 groups for clinical onset and life-span. Mutations in NDUFS1 were linked to a worse clinical course with earlier onset and earlier death. Conclusions: Genotype-phenotype correlations in patients with mutations affecting the genes that encode the electron input module of complex I vary, but patients with NDUFS1 mutation tend to have a worse clinical course than patients with NDUFV1 mutation. Identifying the mutations is of importance for accurate prognostic information and genetic counseling.
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| 2. |
- Sofou, Kalliopi, et al.
(författare)
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A multicenter study on Leigh syndrome: disease course and predictors of survival.
- 2014
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Ingår i: Orphanet journal of rare diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients.
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| 3. |
- Sofou, Kalliopi
(författare)
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Genotypic and phenotypic spectrum of mitochondrial diseases with focus on early onset mitochondrial encephalopathies
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Early-onset mitochondrial encephalopathies comprise a challenging group of neurodegenerative disorders. This is due to their progressive nature, often leading to major disability and premature death, as well as their diagnostic complexity and lack of customized treatments. The overall aim of the research presented in this thesis was to explore the phenotypic and genotypic spectrum of childhood-onset mitochondrial diseases with central nervous system involvement. The present thesis focuses on early-onset mitochondrial encephalopathies with particular emphasis on Alpers and Leigh syndromes. We studied 19 patients with Alpers syndrome and showed specific genotype-phenotype correlations depending on the presence or not of POLG1 mutations. We have further identified, with the help of whole exome sequencing, mutations in NARS2 and PARS2 in two of our patients with Alpers syndrome not associated to POLG1, being the first to link mutations in these genes to human disease and to Alpers syndrome. We also present the natural history data on a unique cohort of 130 patients with Leigh syndrome, along with predictors of long-term outcomes. Disease onset before six months of age, failure to thrive, brainstem lesions on neuroimaging and intensive care treatment were associated with poorer survival. Based on the findings from this study, we suggest revised diagnostic criteria for Leigh syndrome. We also studied the brain MRIs of 66 patients with mitochondrial disorders with central nervous system involvement. We describe the optimal use of brain neuroimaging in the diagnostic work-up of suspected mitochondrial disorders, as well as its role in the differential diagnosis among mitochondrial encephalopathies and from other diseases with similar features. This thesis advances our knowledge of the phenotypic and genotypic spectrum of early-onset mitochondrial encephalopathies and discusses the applicable diagnostic methods, from the diagnostic criteria used to define clinical syndromes, to the role of the traditional and modern methodologies in the diagnostic work-up of these complex disorders. The study of patients with Leigh syndrome is the first joint research work between eight centers from six European countries specializing in mitochondrial diseases, creating a strong platform for ongoing collaboration on mitochondrial research projects.
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| 4. |
- Sofou, Kalliopi
(författare)
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Mitochondrial Disease: A Challenge for the Caregiver, the Family, and Society
- 2013
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Ingår i: Journal of Child Neurology. - : SAGE Publications. - 0883-0738 .- 1708-8283. ; 28:5, s. 663-667
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial diseases represent a genetically and clinically heterogeneous group of inherited metabolic disorders, often resulting in poor functional and survival outcomes for the patient and considerable psychosocial distress for the caregiver. The systematic review undertaken in the present paper emphasizes the critical role of the caregiver in the management of a child with mitochondrial disease, with focus on the burden of mitochondrial disease on the caregiver, the family, and society.
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| 5. |
- Sofou, Kalliopi, et al.
(författare)
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MRI of the brain in childhood-onset mitochondrial disorders with central nervous system involvement.
- 2013
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Ingår i: Mitochondrion. - : Elsevier BV. - 1872-8278 .- 1567-7249. ; 13:4, s. 364-371
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Tidskriftsartikel (refereegranskat)abstract
- We retrospectively studied the brain MRIs of 66 pediatric patients with mitochondrial disorder with central nervous system involvement. Forty-one patients had an identified genetic etiology. A predominance of cerebrocortical lesions was mainly seen in patients with MELAS and Alpers syndrome. Basal ganglia were predominantly affected in patients with Leigh syndrome. All patients with leukoencephalopathy had pathological spectroscopy. Cerebrocortical atrophy with agenesis/atrophy of the corpus callosum was seen in patients with congenital lactic acidosis with or without pyruvate dehydrogenase complex deficiency. The diagnostic approach used in our study - from the neuroanatomical/neurofunctional lesion to disease identification - assists the physician in the use of brain neuroimaging early in the diagnostic work-up of suspected mitochondrial disorders.
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| 6. |
- Sofou, Kalliopi, et al.
(författare)
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Phenotypic and genotypic variability in Alpers syndrome.
- 2012
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Ingår i: European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. - : Elsevier BV. - 1532-2130. ; 16:4, s. 379-89
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Tidskriftsartikel (refereegranskat)abstract
- Alpers syndrome is one of the most common phenotypes of mitochondrial disorders in early childhood and has been associated with pathogenic mutations in POLG1.
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