Search

Moznost provést molekulárne genetické potvrzení dia shy;gnózy ACY1D má zásadní vyznam pro rodinu postizeného probanda. Vázená redakce, deficit aminoacylázy 1 (ACY1D) (MIM 609924) patrí mezi vzácné dedicné poruchy metabolizmu a je charakterizován zvysenym vylucováním N-acetylovanych aminokyselin do moci (serin, kyselina glutamová, alanin, methionin, glycin, leucin a valin). V Centru molekulární bio shy;logie a genetiky Interní hemato-onkologické kliniky FN Brno byla provedena analyza DNA genu I ACY1 i pomocí panelového sekvenování nové generace (target sequencing) s vyuzitím SeqCap EZ Choice Library (Roche Nimble-Gene, Madison, WI, USA) na platforme Illumina. [Extracted from the article]

Dominant optic atrophy (DOA) is an autosomal dominant disorder manifest--ing by slowly progres-sive painless bilateral visual acuity loss with variable degree of severity. DOA is caused by mutations in nuclear DNA encod--ing proteins as-sociated with the in-ner mitochondrial membrane. Most individuals with DOA harbour a dis-ease-caus--ing mutation in the OPA1 gene; however, other genes and loci as-sociated with DOA have also been identified. First symp-toms usual-ly manifest in the first two decades of life. The dis-ease mechanism lies in neurodegenerative damage of retinal ganglion cel-ls lead--ing to optic nerve atrophy. Decrease of visual acuity is as-sociated with colour vision alterations and central or paracentral visual field defects. On fundoscopic examination, optic head nerve pal-lor can be noticed, occasional-ly with excavation. Extraocular symp-toms are present in some patients, caus--ing so-cal-led DOA plus syndrome. Bilateral sensorineural hear--ing los-s, is the most common one; chronic progres-sive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like disorder, and spastic paraplegia of lower limbs are rare. Cur-rently, there is no ef-fective treatment available that would prevent the development of visual impairment. Genetic dia-gnostics and fol-low-up of patients with DOA are held in the Centre for Patients with Mitochondrial Optic Neuropathies, General University Hospital in Prague. The aim of this review is to increase awareness of the most com-mon genetical-ly determined optic neuropathy. [ABSTRACT FROM AUTHOR]

Leber hereditary optic neuropathy (LHON) is maternal ly inherited disorder characterized by subacute loss of vision due to impairment of retinal ganglion cel ls eventual ly lead ing to optic atrophy. Three prevalent point mutations in mitochondrial DNA: m.11778G>A, m.3460G>A, and m.14484T>C, are causative in the majority (> 95%) of cases. All of these mutations aff ect one of the subunits of complex I, NADH-ubiquinone oxidoreductase, the fi rst enzyme of the mitochondrial respiratory chain. The presence of a mutation is neces sary but not suffi cient to cause visual los s. The penetrance is incomplete with only about 50% of men and 10% of women event. develop ing clinical signs of the dis ease. Recently, it was proven that early initiation of ther apy with idebenone in patients manifest ing LHON ameliorates visual functions and clinical trials test ing several other promis ing ther apies are underway. Incomplete penetrance, similarites with other disorders affect ing the optic nerve and a great variability of clinical features cause considerable dia gnostic diffi culties. Often there is a delay in ther apy initiation, as late as in the phase of the ir reversible optic nerve damage. In 2013, we established a multidisciplinary medical care centre dedicated to patients with mitochondrial optic neuropathies in General University Hospital in Prague to develop eff ective diagnostic and treatment algorithms and to study the underlying pathogenetic mechanisms. [ABSTRACT FROM AUTHOR]