To report the RRM2B mutation frequency in adults with multiple mtDNA deletions and examine RNR assembly in a patient with Kearns-Sayre syndrome (KSS) caused by two novel RRM2B mutations.
To report the RRM2B mutation frequency in adults with multiple mtDNA deletions and examine RNR assembly in a patient with Kearns-Sayre syndrome (KSS) caused by two novel RRM2B mutations.
Our genetic and metabolomics analyses suggest that CAFSA is a heterogeneous entity related to mitochondrial DNA alterations either through POLG mutations or a mechanism similar to what is observed in Kearns-Sayre syndrome.
Cerebellar ataxia is common in myoclonic epilepsy with ragged red fibers (MERFF) due to mutations in the mitochondrial transfer RNA (tRNA) lysine gene, in Kearns-Sayre syndrome due to mtDNA deletions, in sensory ataxic neuropathy with dysarthria and ophthalmoplegia (SANDO) due to nuclear POLG1 gene mutations, and also in ARCA2, Friedreich's ataxia, SPG7, SCA28 and autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) due to mutations in nuclear genes involved in mitochondrial morphology or function.
These predominant breakpoint regions are similar to those described in other conditions with multiple deletions, such as autosomal dominant progressive external ophthalmoplegia (adPEO) and normal aging, but different from those described in diseases due to single deletions such as Kearns-Sayre syndrome and sporadic PEO.
These predominant breakpoint regions are similar to those described in other conditions with multiple deletions, such as autosomal dominant progressive external ophthalmoplegia (adPEO) and normal aging, but different from those described in diseases due to single deletions such as Kearns-Sayre syndrome and sporadic PEO.
At follow-up, HSS was to 89.7 in the FuZion® group and 89.0 in the standard group, KSS (clinical) was 92.6 in and 91.3 respectively, and KSS (Functional) was 91.0 in the FuZion® group and 87.6 in the standard group.
At follow-up, HSS was to 89.7 in the FuZion® group and 89.0 in the standard group, KSS (clinical) was 92.6 in and 91.3 respectively, and KSS (Functional) was 91.0 in the FuZion® group and 87.6 in the standard group.
At follow-up, HSS was to 89.7 in the FuZion® group and 89.0 in the standard group, KSS (clinical) was 92.6 in and 91.3 respectively, and KSS (Functional) was 91.0 in the FuZion® group and 87.6 in the standard group.
At follow-up, HSS was to 89.7 in the FuZion® group and 89.0 in the standard group, KSS (clinical) was 92.6 in and 91.3 respectively, and KSS (Functional) was 91.0 in the FuZion® group and 87.6 in the standard group.
At follow-up, HSS was to 89.7 in the FuZion® group and 89.0 in the standard group, KSS (clinical) was 92.6 in and 91.3 respectively, and KSS (Functional) was 91.0 in the FuZion® group and 87.6 in the standard group.
Probands were suspected to have atypical Kearns-Sayre syndrome, but were diagnosed with combined oxidative phosphorylation deficiency-20 due to a novel suspected missense variant (c.1691C>T, p.Ala564Val) in VARS2.
Five of them harbored mtDNA deletions associated with Kearns-Sayre syndrome (KSS), one had a mitochondrial point mutation at the mtDNA ATPase6 gene, and one had a POLG mutation.
Cerebellar ataxia is common in myoclonic epilepsy with ragged red fibers (MERFF) due to mutations in the mitochondrial transfer RNA (tRNA) lysine gene, in Kearns-Sayre syndrome due to mtDNA deletions, in sensory ataxic neuropathy with dysarthria and ophthalmoplegia (SANDO) due to nuclear POLG1 gene mutations, and also in ARCA2, Friedreich's ataxia, SPG7, SCA28 and autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) due to mutations in nuclear genes involved in mitochondrial morphology or function.
Besides demonstrating remarkable similarities in the lesion profile of KSS and FL-PGC-1a-deficient mice, this study first provides morphological evidence for the identical origin of WM and GM vacuolation as well as for the presence of intracytoplasmic oligodendroglial vacuoles in mitochondriopathies.
Histopathological comparison of Kearns-Sayre syndrome and PGC-1α-deficient mice suggests a novel concept for vacuole formation in mitochondrial encephalopathy.