[Diagnostic criteria: OCT angiography for retinal angiomatous proliferation (RAP lesions, type 3 neovascularization)]. / Diagnostische Kriterien: OCT­Angiographie bei retinalen angiomatösen Proliferationen (RAP­Läsionen, Typ­3-Neovaskularisationen).

BACKGROUND: Multimodal imaging of retinal angiomatous proliferation (RAP) lesions (type 3 neovascularization) and the diagnostic significance of optical coherence tomography angiography (OCT-A). MATERIAL AND METHODS: Confirmation of the diagnosis in six case reports with fundus photography, optical coherence tomography (OCT), fluorescein angiography (FLA), indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCT­A). RESULTS AND CONCLUSION: The use of OCT­A is helpful for the diagnosis and follow-up examinations of RAP lesions (type 3 neovascularization). It enables the detailed visualization of intraretinal and choroidal microcirculation. Furthermore, it is possible to evaluate the progression, classify the stages and comprehend the treatment strategy.

[Multimodal imaging in Goldmann-Favre syndrome]. / Multimodale Bildgebung beim Goldmann-Favre-Syndrom.

Case report of a 23-year-old male patient suffering from Goldmann-Favre syndrome. The patient reported bilateral visual loss since 10 years of age and difficulties with dark adaptation for 2 years. Until recently a final diagnosis was not found. Multimodal imaging using multicolor fundus imaging (MCFI), optical coherence tomography (OCT), fundus autofluorescence (FAF), fluorescein angiography (FLA), electroretinography (ERG) and visual evoked potential (VEP) confirmed the diagnosis. We describe multimodal imaging of this rare hereditary retinal dystrophy. For diagnosis of Goldmann-Favre syndrome a multimodal examination is helpful. To confirm the diagnosis a genetic analysis is necessary.

Tuberous sclerosis presenting in late adult life.

A 59 year old woman presented with a three year history of left sided weakness. Magnetic resonance imaging of the brain showed a large high signal lesion occupying most of the right temporal lobe with mass effect. A probable diagnosis of low grade glioma led to temporal lobectomy. Histology revealed dysplastic cortical morphology typical of tuberous sclerosis. There were no clinical signs or family history of the disease. Ultrasound showed multiple bilateral renal angiomyolipomas, confirming the diagnosis of tuberous sclerosis. Molecular genetic analysis of peripheral white blood cells identified a novel mis-sense mutation R1409W in exon 33 of the TSC2 gene.

Epigenetic modification and uniparental inheritance of H19 in Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome associated with a characteristic pattern of visceromegaly and predisposition to childhood tumours. BWS is a genetically heterogeneous disorder; most cases are sporadic but approximately 15% are familial and a small number of BWS patients have cytogenetic abnormalities involving chromosome 11p15. Genomic imprinting effects have been implicated in familial and non-familial BWS. We have investigated the molecular pathology of 106 sporadic BWS cases; 17% (14/83) of informative cases had uniparental disomy (UPD) for chromosome 11p15.5. In each case UPD appeared to result from a postzygotic event resulting in mosaicism for segmental paternal isodisomy. The critical region for isodisomy was refined to a 25 cM interval between D11S861 and D11S2071 which contained the IGF2, H19, and p57(KIP2) genes. In three cases isodisomy for 11q markers was detected but this did not extend further than 11q13-q21 suggesting that complete chromosome 11 disomy may not produce a BWS phenotype. The allele specific methylation status of the H19 gene was investigated in 80 sporadic BWS cases. All 13 cases with UPD tested displayed hypermethylation consistent with an excess of paternal H19 alleles. In addition, five of 63 (8%) cases with normal biparental inheritance had H19 hypermethylation consistent with an "imprinting centre" mutation (ICM) or "imprinting error" (IE) lesion. The phenotype of patients with putative ICM/IE mutations was variable and overlapped with that of non-UPD sporadic BWS cases with normal H19 methylation. However, exomphalos was significantly (p < 0.05) more common in the latter group. These findings may indicate differential effects on the expression of imprinted genes in chromosome 11p15 according to the precise molecular pathology. Analysis of H19 methylation is useful for the diagnosis of both UPD or altered imprinting in BWS and shows that a variety of molecular mechanisms may cause relaxation of IGF2 imprinting in BWS.

Effect of alpha thalassaemia trait and enhanced gamma chain production on disease severity in beta thalassaemia major and intermedia.

One hundred and twenty patients with homozygous beta thalassaemia were selected to determine the clinical effects of certain genetic factors which may modify disease severity. Genetic analysis defined specific beta thalassaemia mutations, the alpha thalassaemia genotype, and the presence of an XmnI restriction enzyme site, associated with increased fetal haemoglobin (HbF) production under certain conditions. Genotypic data with globin chain synthesis were related to the age when regular transfusions began and subsequent pubertal development. This study showed that the major determinants of disease severity in beta thalassaemia were the beta thalassaemia mutations, with co-inheritance of alpha thalassaemia trait and coinheritance of a high HbF determinant acting as ameliorating factors. The presence of an alpha thalassaemia deletion significantly reduced initial disease severity, although the effect on pubertal development was less clear. It is concluded that detailed genetic analysis should be performed in all newly diagnosed patients with thalassaemia. This, in conjunction with clinical assessment, will help to predict disease severity and prognosis.

The spectrum of beta thalassaemia mutations in the UAE national population.

The beta thalassaemia alleles in 50 beta thalassaemia heterozygotes originating from many parts of the United Arab Emirates (UAE) have been characterised using the allele specific priming technique of the polymerase chain reaction (PCR). The IVSI-5 (G-->C) mutation was found to be present in 66%, while six other alleles occurred at the much lower frequencies of 2% to 8%. These were codon 8/9 (+G), IVSI-1, 3' end (-25 bp), codon 5 (-CT), IVSII-1 (G-->A), codon 30 (G-->C), and codon 15 (G-->A). The mutation types and percentages are compared with other Mediterranean Arab countries and neighbouring areas. It is proposed that IVSI-5 and other Asian Indian mutations were introduced into the UAE by population migration from the region previously known as Baluchistan. These findings should be useful for genetic counselling and the development of a first trimester prenatal diagnosis programme based on direct detection of mutations in the UAE.