A Novel Recessive RPGRIP1 Mutation Causing Leber Congenital Amaurosis.

BACKGROUND: Leber congenital amaurosis is an early-onset childhood severe retinal dystrophy, of significant genetic heterogeneity. RPGRIP1 is ubiquitously expressed, but mutations in RPGRIP1 lead to a retina-restricted phenotype, such as Leber congenital amaurosis and cone-rod dystrophy. PATIENT AND METHODS: We analysed a consanguineous family from Egypt in which one individual, a four-year-old girl, was affected with Leber congenital amaurosis. IROme, a proprietary enrichment system for retinal dystrophy genes, was applied and high throughput sequencing was performed. RESULTS: Severe visual impairment was reported during infancy. The fundus of the affected patient exhibited disc pallor and attenuated vessels. Neurodevelopmental delay and brain atrophy in the CT scan were reported. Genomic sequencing identified a novel homozygous deletion, c.[420delG], in RPGRIP1. This mutation was not detected in 80 ethnically matched controls and has not been reported elsewhere. CONCLUSIONS: Identifying new mutations in Leber congenital amaurosis-related genes and their clinical manifestations can improve our understanding of the disease and could help to stratify the population for potential therapies.

Cone-rod dystrophy caused by a novel homozygous RPE65 mutation in Leber congenital amaurosis.

BACKGROUND: The aim of this study was to describe an unexpected phenotype in a family with Leber congenital amaurosis (LCA) due to a retinal pigment epithelium-specific protein 65 kDa (RPE65) homozygous mutation. HISTORY AND SIGNS: We analyzed a family from Yemen in which 3 individuals were affected with LCA. Linkage analysis using markers flanking the known LCA genes was done, followed by direct sequencing of RPE65. THERAPY AND OUTCOME: Severe visual impairment and night blindness were observed during infancy. We observed photophobia only in the 8-year-old patient. The youngest affected had bilateral hyperopia of +3.50 and visual acuity of 1/60. The oldest two had visual acuity limited to hand movements in the right eye (OD) and counting fingers in the left eye (OS) for the oldest and of 5/60 OD, 6/60 OS for the other. They showed disc pallor, attenuated vessels, white flecks in the retina mid-periphery and bull's eye maculopathy. ERGs of the oldest child were completely unresponsive. Genomic sequencing identified a novel homozygous missense mutation, IVS2-3C>G, in the second RPE65 intron. CONCLUSIONS: We identified a novel LCA-related homozygous RPE65 mutation associated with a severe clinical presentation including an early and severe cone dysfunction. This is in contrast with the presentation associated with other RPE65 mutations predominantly causing rod-cone dystrophy with residual visual function.

Spontaneous intracranial haemorrhage in children with chronic immune thrombocytopenic purpura.

Spontaneous intracranial haemorrhage (ICH) is a rare complication of chronic immune thrombocytopenic purpura (ITP) in children. We report four patients with cITP who developed ICH. The latency between onset of ITP and ICH varied from 1-8 years. All our patients were profoundly thrombocytopenic (platelet count of <10 x 109/l) at the time of their intracranial bleed. The presenting features and management are discussed. All patients survived, three had complete neurological recovery while one had a minimal residual neurological deficit.

Mild autosomal recessive osteopetrosis: successful treatment with bone marrow transplant.

We describe a 5 1/2 year old boy who was diagnosed with mild autosomal recessive osteopetrosis based on the presence of bony sclerosis, extramedullary haematopoeisis, leukoerythroblastosis and visual impairment who had an allogeneic bone marrow transplant from a matched sibling donor. Conditioning regime was busulphan 16 mg/kg and cyclophosphamide 200 mg/kg. Apart from transient hypercalcaemia, there were no major post transplant complications. Four years post transplant, the extramedullary haematopoeisis has resolved completely with normal blood counts. Apart from a fracture after a trivial fall two months after transplant, he has not suffered any fracture related limb deformities.

Controlled hypotension in adults undergoing choroidal melanoma resection: comparison between the efficacy of nitroprusside and magnesium sulphate.

BACKGROUND AND OBJECTIVE: To determine whether magnesium sulphate could induce controlled hypotension, reduce choroidal blood flow, provide a 'dry' operative field and could be compared with sodium nitroprusside in the recently raised issue of the use of hypotensive anaesthesia in eye surgery, i.e. for choroidal tumour surgery as the choroid is the most fragile and vascular structure in the eye. METHODS: Forty adult patients undergoing choroidal melanoma resection and anaesthetized with 2.5 mg kg(-1) propofol, followed by a constant infusion of 120 microg kg(-1) min(-1), and remifentanil 1 microg kg(-1), followed by a continuous infusion of 0.25 microg kg(-1) min(-1), were randomly assigned to two groups to receive either magnesium sulphate or sodium nitroprusside. RESULTS: Controlled hypotension was achieved at the target systolic pressure of 80 mmHg within 107 +/- 16 and 69 +/- 4.4 s for magnesium sulphate and sodium nitroprusside, respectively. Choroidal blood flow decreased by 24 +/- 0.3% and 22 +/- 3.3% for magnesium sulphate and sodium nitroprusside, respectively. Controlled hypotension was sustained in both groups throughout surgery, and the surgical field rating decreased in a range of 80% in both groups. Sodium nitroprusside decreased pH and increased PaCO2. There were no postoperative complications in any of the groups. CONCLUSION: Magnesium sulphate controlled hypotension, reduced intraoperative pressure and provided good surgical conditions for choroidal melanoma resection with no need for additional use of a potent hypotensive agent in adults.