A novel LAMB2 gene mutation associated with a severe phenotype in a neonate with Pierson syndrome.

BACKGROUND: Pierson syndrome (PS) is a rare autosomal recessive disorder, caused by mutations in the laminin ß2 (LAMB2) gene. It is characterized by congenital nephrotic syndrome, microcoria, and neurodevelopmental deficits. Several mutations with genotype-phenotype correlations have been reported, often with great clinical variability. We hereby report a novel homozygous nonsense mutation in the LAMB2 gene, associated with a severe phenotype presentation. CASE DIAGNOSIS: We describe a term male infant born from consanguineous parents. The mother previously lost three children in the neonatal period, secondary to undefined renal disease, had two spontaneous abortions, and gave birth to one healthy daughter. The index case presented at birth with bilateral microcoria, severe hypotonia, respiratory distress, and congenital nephrotic syndrome associated with anuria and severe renal failure requiring peritoneal dialysis. The patients' clinical follow-up was unfavorable, and the newborn died at 7 days of life, after withdrawal of life support. Genetic analysis revealed a homozygous nonsense mutation at position c.2890C>T causing a premature stop codon (p.R964*) in LAMB2 gene. CONCLUSION: We here describe a novel nonsense homozygous mutation in LAMB2 gene causing a severe neonatal presentation of Pierson syndrome. This new mutation expands the genotype-phenotype spectrum of this rare disease and confirms that truncating mutations might be associated with severe clinical features.

Anterior segment indocyanine green angiography in anterior scleritis and episcleritis.

OBJECTIVE: To evaluate the pattern of anterior segment indocyanine green (ICG) angiography in episcleritis and scleritis. DESIGN: Prospective comparative (paired-eye) observational case series. PARTICIPANTS: Twenty subjects presenting clinical diseases compatible with episcleritis or scleritis. METHODS: Anterior segment ICG angiography was performed according to a standard protocol in subjects presenting either episcleritis or scleritis. Photographs of the anterior segment were taken in the early phase (up to 3 minutes after dye injection), intermediate phase (10-12 minutes) and late phase (30-45 minutes). The inflamed zones were compared with the same regions of the controlateral eye. The amount of protein ICG exudation was scored by a masked observer as follows: zero for no exudation, one for slight exudation, two for moderate exudation, and three for severe exudation. MAIN OUTCOME MEASURES: Evaluation of dye leakage, which reflects protein exudation, with anterior segment ICG angiography in episcleritis and scleritis. RESULTS: Twenty subjects with a mean age of 43 +/- 15 years (7 male, 13 female) were enrolled in the study. Thirteen subjects had anterior scleritis (7 nodular, 5 diffuse, and 1 scleromalacia perforans), and 7 subjects had episcleritis. Only 1 out of 7 subjects with episcleritis showed a slight ICG leakage (a score of one), whereas all subjects with scleritis had ICG leakage scores of one or more (P = 0.0005, Fisher exact test). CONCLUSIONS: ICG angiography of the anterior segment of the eye is a good clinical test to differentiate episcleritis from scleritis.

Ocular motility in genetically defined autosomal dominant cerebellar ataxia.

PURPOSE: To describe ocular motility in patients having genetically characterized dominant cerebellar ataxia. DESIGN: Observational case series. METHOD: Nine ataxic adults having the following molecular genetic diagnoses underwent ophthalmic examination and ocular motility recordings: four with spinocerebellar ataxia type 6 (SCA-6), three with SCA-3, one with SCA-1, and one with episodic ataxia type 2 (EA-2). RESULTS: Versions were normal in eight patients. Most were orthotropic, but one with SCA-3 had exotropia at near. The near point of convergence was remote in five patients. Eight of nine patients had horizontal nystagmus evoked by lateral gaze. All patients with SCA-6 had downbeat nystagmus. Downbeat nystagmus was absent in SCA-1, SCA-3, and EA-2. Three patients with SCA-6 and one with EA-2 had symptomatic improvement when treated with acetazolamide. CONCLUSION: Patients with genetically defined dominant cerebellar ataxia generally had normal binocular alignment and versions and only mild vergence impairment. Downbeat nystagmus was strongly associated with the SCA-6 mutation, whose associated episodes of dizziness and imbalance may be relieved by acetazolamide.