During endocytosis, clathrin and the clathrin adaptor protein AP-2 (ref. 1), assisted by a variety of accessory factors, help to generate an invaginated bud at the cell membrane,. One of these ...factors is Eps15, a clathrin-coat-associated protein that binds the α-adaptin subunit of AP-2 (refs 4-8). Here we investigate the function of Eps15 by characterizing an important binding partner for its region containing EH domains; this protein, epsin, is closely related to the Xenopus mitotic phosphoprotein MP90 (ref. 10) and has a ubiquitous tissue distribution. It is concentrated together with Eps15 in presynaptic nerve terminals, which are sites specialized for the clathrin-mediated endocytosis of synaptic vesicles. The central region of epsin binds AP-2 and its carboxy-terminal region binds Eps15. Epsin is associated with clathrin coats in situ, can be co-precipitated with AP-2 and Eps15 from brain extracts, but does not co-purify with clathrin coat components in a clathrin-coated vesicle fraction. When epsin function is disrupted, clathrin-mediated endocytosis is blocked. We propose that epsin may participate, together with Eps15, in the molecular rearrangement of the clathrin coats that are required for coated-pit invagination and vesicle fission.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Posterior Column Ataxia and Retinitis Pigmentosa (PCARP) is an autosomal-recessive neurodegenerative syndrome. Standard phenotype expected: areflexia and retinitis pigmentosa in infancy; night ...blindness and peripheral visual field loss in late childhood; evaluation to sensory ataxia secondary to degeneration of the posterior columns of the spinal cord. We reported a case of 3 yrs old children with PCARP secondary to FLVCR1 mutation and atypical phenotype. Our patient have a congenital and progressive acro-osteolysis of fingers and precocious ataxia with general hypotonia, and deep tendon reflex absent in the legs. No visual impairment was reported and the fundus oculi was normal. ERG was normal. Nerve conduction study showed sensory peripheral neuropathy. Median-nerve SEPs were not recordable for sensitive neuropathy. Brain and total spinal cord MRI was normal. Genetic study showed a truncated FLVCR1 protein by mother and new potentially pathogenetic mutation by father. Sensory peripheral neuropathy was reported in only few cases of PCARP.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Mutations in genes encoding subunits of the tRNA-splicing endonuclease (TSEN) complex were identified in patients with pontocerebellar hypoplasia 2 (PCH2) and pontocerebellar hypoplasia 4 (PCH4).
We ...report molecular genetic findings in 12 Italian patients with clinical and MRI findings compatible with PCH2 and PCH4.
We retrospectively selected a cohort of 12 children from 9 Italian families with MRI of hypoplastic pontocerebellar structures and clinical manifestations suggesting either PCH2 or PCH4 and submitted them to direct sequencing of the genes encoding the 4 subunits of the TSEN complex, namely TSEN54, TSEN34, TSEN15, and TSEN2.
In a cohort of 12 children, we detected the common p.A307S mutation in TSEN54 in 9/12 available patients from nine unrelated families. We also detected a novel c.1170_1183del (p. V390fs39X) in compound heterozygosity with the common p.A307S in a child with a severe PCH4 phenotype. In another severely affected patient, the second mutant allele was not identified. Two sibs without mutations in the TSEN complex were unlinked to the PCH3 locus. In addition to typical clinical and neuroradiologic features of PCH2, both children were affected by a tubulopathy resembling Bartter syndrome.
We confirm that the common p.A307S mutation in TSEN54 is responsible for most of the patients with a PCH2 phenotype. The presence of a heterozygous in/del variant correlates with a more severe phenotype as PCH4. In addition, we describe a new clinical form of PCH in 2 sibs with clinical and MRI features of PCH2.
Abstract Forty-five consecutive subjects (26M, 19F; mean age 54 ± 14 yrs) with a diagnosed retinal vein occlusion (RVO), were followed-up for 8 yrs. As many as 145 sex-age- and blood pressure-matched ...individuals (78M, 67F; mean age 54.4 ± 13.5 yrs), that did not experience any vascular event, served as controls. At the time of the RVO, controls and subjects did not differ as to hypercholesterolemia, hypertrigliceridemia, diabetes mellitus, smoking habits, inherited/acquired thrombophilia. At the follow-up completion, they differed as to statin consumption ( p = 0.016). During the 8-yrs follow-up, in the control population, 11 out of 145 (7.6%) subjects had experienced a major vascular event (8 coronary artery disease; 3 cerebral non-fatal ischemic stroke). In contrast, of the 45 subjects with a history of RVO, as many as 10 (22.2%) had experienced a major vascular event: 4 coronary artery disease; 4 cerebral non-fatal ischemic stroke; 2 cardiovascular + cerebrovascular event ( p = 0.012). A prolonged antiplatelet treatment, prior to the major vascular event, was found in 5/45 cases (11.1%) vs 23/145 (15.9%) controls ( p = 0.63). In contrast, a long-lasting administration of anti-hypertensive drugs, to achieve a control of blood pressure, was found in 83.4% of controls and only in 46.7% of cases ( p < 0.0001). In conclusion, in a 8-yr follow-up, coronary artery disease and/or non-fatal ischemic stroke were more common in subjects with a history of RVO than in a large setting of subjects comparable for cardiovascular risk factors. These data also argue for RVO as a vascular disease in which aggressive anti-hypertensive therapy to prevent stroke and/or myocardial infarction is needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Few studies reported that subcortical N13b and P13 components are more sensitive than the conventional method (N20 and the CCT) to detect high cervical cord compression. P13 and N13b are considered ...both as peaks generated at the cranio-cervical junction, but in clinical neurophysiological practice only P13 is evaluate. We report our laboratory experience on N13b-P13 components in pediatric subjects with cranio-cervical junction alteration of different etiologies. We study both asymptomatic and symptomatic pediatric subjects with relative brain and cervical cord MRI alterations. Our data shows that N13b and P13 are both sensitive and specific to detect compressive myelopathy at cranio-cervical junction. N13b is a signal to be recorded easily repeatable and sometimes more stable compared to the P13 and can be useful for studying selected cases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The aim of this study is to evaluate Brainstem Auditory Evoked Potentials (BAEPs) in perinatal asphyxtic infants, performed during and/or after therapeutic hypothermia (TH). A group of 27 patients ...enrolled for TH secondary to perinatal asphyxiated performed BAEPs: 8 pt during and after TH; 8 pt during TH and 11 pt only after TH. For all BAEPS absolute latency and Interpeak latencies (IPL) were evaluated. One patient, died after TH, showed absence of all bilateral waves. Another patient showed monolateral absence of III–V waves. The other 25 patients showed normal BAEPS. Patients, who performed BAEPS during and after TH (7 pt), presented a significant reduction of absolute latency and IPL after TH. Cooling seems to increase absolute and interpeak latencies of Brainstem Evoked Potentials, regarding peripheral VIII nerves and central generators.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Somatosensory evoked potentials(SEPs) and EEG are reliable outcome predictors of coma after cardiac arrest (CA). Nevertheless, only few multicentric studies are available. Aim of the study was to ...evaluate the prognostic value of EEG and SEPs association in post-anoxic comatose patients at different recording time from cardiac arrest (CA) in an Italian multicentric study. Comatose patients after CA treated with TH were included. EEG and SEPs were recorded within 12 h and at 72 h after CA. EEG was classified into “non-continuous” and “continuous”. SEPs were dichotomized into “bilaterally absent” (BA) and “present”. Neurologic outcome was evaluated at 6 months by GOS: “awakening”(GOS 3–5) was considered good outcome. 83 patients were included to date. “Continuous” EEG pattern at 12 h always predicted good outcome, “non-continuous” pattern at 72 h always predicted poor outcome. BA SEPs always predicted poor outcome. Early “continuous” EEG pattern was always associated with present SEPs. SEPs provide a specific and time-independent predictor of poor outcome. EEG provide a specific and time-dependent predictor of good outcome (at <12 h) and poor outcome (at 72 h). Early “continuous” EEG and BA SEPs are never associated together. Combined EEG/SEPs recordings are a useful tool for reliable prognostication both of good and poor outcome in comatose patients treated with TH.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The role of SEPs in motor prognosis of hypoxic–ischemic neonatal encephalopathy has been evaluated in pre-hypothermia era (Suppiej, 2010) but their role in babies treated with hypothermia has not ...been studied yet. We investigated motor outcome at 12 months of age in 38 children who suffered from hypoxic–ischemic neonatal encephalopathy and were treated with hypothermia at the NICU of the Paediatric University Hospital of Padua. All performed median nerve SEPs in the neonatal period, traces were scored as bilaterally present (group1) or as bilaterally/unilaterally absent (group2) cortical N20 response. At follow up 4/38 children had the diagnosis of cerebral palsy (all of them had bilaterally absent cortical SEP). Of the remaining 34, 7 had abnormal (<5°) scores at the motor subscales of the Griffith’s Scale. A significant difference was found between motor scores of group 1 (mean 97 DS 13) and group2 (mean 82 SD 14) ( p = .023 Mann–Whitney test). Data seem to suggest a prognostic value of SEPs to predict neuromotor outcome as evaluated with Griffiths Scale at one year of age. However, these results need to be confirmed at 24 months of age when clinical prognosis is known to be more reliable.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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