specialista in oculistica

Changes in the optic disc excavation of children affected by cerebral visual impairment: a tomographic analysis.

Early onset, non fluctuating spinocerebellar ataxia and a novel missense mutation in CACNA1A gene.

CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia.

Oculomotor dysfunction in cerebral visual impairment following perinatal hypoxia.

Changes in the optic disc excavation of children affected by cerebral visual impairment: a tomographic analysis.
Ruberto G, Salati R, Milano G, Bertone C, Tinelli C, Fazzi E, Guagliano R, Signorini S, Borgatti R, Bianchi A, Bianchi PE.Invest Ophthalmol Vis Sci. 2006 Feb;47(2):484-8.PMID: 16431940

PURPOSE: To obtain quantitative data on the optic disc excavation in children affected by cerebral visual impairment (CVI) by using the Heidelberg Retinal Tomograph (HRT)-II (Heidelberg Engineering, Heidelberg, Germany).
METHODS: A total of 24 subjects affected by CVI (mean age, 7.28 years) were examined: 16 in alert conditions and 8 under general anesthesia. The following parameters of the optic nerve head were examined: disc area, cup area, rim area, cup volume, rim volume, cup-to-disc area ratio, mean cup depth, maximum cup depth, cup shape measure, and mean retinal nerve fiber layer (RNFL) thickness. The tomographic results in children with CVI were compared with those of 88 normal, alert subjects of similar age.
RESULTS: The optic disc of patients with CVI appeared smaller than normal. Its excavation, however, was more pronounced. Several tomographic parameters were altered in CVI-affected subjects. Statistical analysis showed a highly significant probability in cup-to-disc area ratio (P < 0.01, both eyes), rim area (P < 0.01, both eyes), cup shape measure (P < 0.01, right eye; P < 0.01, left eye), and mean RNFL thickness (P < 0.01, right eye; P < 0.01, left eye). A novel observation was temporal atrophy of the optic nerve head in CVI.
CONCLUSIONS: The data provide a tridimensional, objective evaluation of the anatomic alterations of the optic nerve head in children with CVI. Furthermore, tomographic standards for optic disc shape in normal children are set for the first time.
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Early onset, non fluctuating spinocerebellar ataxia and a novel missense mutation in CACNA1A gene.
Tonelli A, D'Angelo MG, Salati R, Villa L, Germinasi C, Frattini T, Meola G, Turconi AC, Bresolin N, Bassi MT.J Neurol Sci. 2006 Feb 15;241(1-2):13-7. Epub 2005 Dec 2.PMID: 16325861 

 Mutations in the brain-specific P/Q type Ca2+ channel alpha1 subunit gene, CACNA1A, have been identified in three clinically distinct disorders, spinocerebellar ataxia type 6 (SCA6), episodic ataxia type 2 (EA2), and familial hemiplegic migraine type 1 (FHM1). SCA6 is associated with small expansions of a CAG repeat at the 3' end of the gene, while point mutations are mostly responsible for its two allelic disorders, FHMI and EA2. From the electrophysiological point of view, while FHMI mutations lead to a gain of function [Tottene A, Fellin T, Pagnutti S, Luvisetto S, Striessnig J, Fletcher C, et al. Familial hemiplegic migraine mutations increase Ca2+ influx through single human CaV2.1 channels and decrease maximal CaV2.1 current density in neurons. Proc Natl Acad Sci 99 (20) (2002) 13284-13289.], EA2 mutations usually generate a loss of channel function [Guida S, Trettel F, Pagnutti S, Mantuano E, Tottene A, Veneziano L, et al. Complete loss of P/Q calcium channel activity caused by a CACNA1A missense mutation carried by patients with episodic ataxia type 2. Am J Hum Genet 68 (3) (2001) 759-764, Wappl E, Koschak A, Poteser M, Sinnegger MJ, Walter D, Eberhart A, et al. Functional consequences of P/Q-type Ca2+ channel Cav2.1 missense mutations associated with episodic ataxia type 2 and progressive ataxia. J Biol Chem 277 (9) (2002) 6960-6966.]. In the present study, we describe a child affected by permanent non-fluctuating limb and trunk ataxia with a quite early age of onset. Interestingly, the size of the CACNA1A triplet repeat region in the patient is within the normal range while he carries a novel de novo missense mutation in this gene, p.R1664Q. Although functional data are not available, based on the literature data indicating that severe reductions in P/Q-type channel activity favour episodic and/or progressive ataxic symptoms [Wappl E, Koschak A, Poteser M, Sinnegger MJ, Walter D, Eberhart A, et al. Functional consequences of P/Q-type Ca2+ channel Cav2.1 missense mutations associated with episodic ataxia type 2 and progressive ataxia. J Biol Chem 2002;277(9):6960-6966.], we hypothesize that the functional consequence of the mutation here identified is a partial loss of the Ca channel function. In conclusion, the clinical and molecular findings reported here suggest the opportunity to screen for point mutation in this gene, even patients with a clinical phenotype for some aspects slightly different from the typical picture more commonly associated to SCA6, EA2 or FHM1 diseases. 

CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia.
Kohl S, Varsanyi B, Antunes GA, Baumann B, Hoyng CB, Jägle H, Rosenberg T, Kellner U, Lorenz B, Salati R, Jurklies B, Farkas A, Andreasson S, Weleber RG, Jacobson SG, Rudolph G, Castellan C, Dollfus H, Legius E, Anastasi M, Bitoun P, Lev D, Sieving PA, Munier FL, Zrenner E, Sharpe LT, Cremers FP, Wissinger B.Eur J Hum Genet. 2005 Mar;13(3):302-8. PMID: 15657609 

 Achromatopsia is a congenital, autosomal recessively inherited disorder characterized by a lack of color discrimination, low visual acuity (<0.2), photophobia, and nystagmus. Mutations in the genes for CNGA3, CNGB3, and GNAT2 have been associated with this disorder. Here, we analyzed the spectrum and prevalence of CNGB3 gene mutations in a cohort of 341 independent patients with achromatopsia. In 163 patients, CNGB3 mutations could be identified. A total of 105 achromats carried apparent homozygous mutations, 44 were compound (double) heterozygotes, and 14 patients had only a single mutant allele. The derived CNGB3 mutation spectrum comprises 28 different mutations including 12 nonsense mutations, eight insertions and/or deletions, five putative splice site mutations, and three missense mutations. Thus, the majority of mutations in the CNGB3 gene result in significantly altered and/or truncated polypeptides. Several mutations were found recurrently, in particular a 1 bp deletion, c.1148delC, which accounts for over 70% of all CNGB3 mutant alleles. In conclusion, mutations in the CNGB3 gene are responsible for approximately 50% of all patients with achromatopsia. This indicates that the CNGB3/ACHM3 locus on chromosome 8q21 is the major locus for achromatopsia in patients of European origin or descent. 
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Oculomotor dysfunction in cerebral visual impairment following perinatal hypoxia.
Salati R, Borgatti R, Giammari G, Jacobson L.Dev Med Child Neurol. 2002 Aug;44(8):542-50. PMID: 12206621

The aim of the study was to describe ocular motility in a sample of 56 patients affected by cerebral visual impairment (CVI) of hypoxic-ischemic origin. The sample consisted of 56 participants (37 males and 19 females), ranging in age from 2 to 16 years. In all cases CVI was associated with MRI-verified damage of the cerebral visual system. A complete ophthalmologic and neurological assessment was performed. Behaviour of gaze was studied in four conditions: during scanning of the surrounding environment, during fixation, execution of saccades, and pursuing. In addition, strabismus, nystagmus, and paroxysmal ocular deviations were evaluated. Ocular motility was studied by video recording the patients' eye motility during orthoptic examination. Each pattern of ocular motility studied revealed profound alterations in all the individuals examined. Typical features of ocular motility in CVI were: paroxysmal ocular deviations (present in 78%); the presence of variable angle strabismus (86%); and defective coordination of saccades (93%). Exploration of the environment and fixation were also impaired (88% and 84%, respectively). Disorders of initiation and performing saccades, absence of smooth pursuit, vergence abnormalities, nystagmus beats, instability of fixation, and difficulty in the systematic exploration of the environment were observed. These abnormalities characterize lack of gaze coordination found in children with brain damage. An early and detailed evaluation of ocular motility in individuals with CVI is important, especially when rehabilitation intervention is intended.