Clinical Characteristics, Mutation Spectrum, and Prevalence of Åland Eye Disease/Incomplete Congenital Stationary Night Blindness in Denmark

PURPOSE: To assess clinical characteristics, foveal structure, mutation spectrum, and prevalence rate of Åland eye disease (AED)/incomplete congenital stationary night blindness (iCSNB). METHODS: A retrospective survey included individuals diagnosed with AED at a national low-vision center from 1980 to 2014. A subset of affected males underwent ophthalmologic examinations including psychophysical tests, full-field electroretinography, and spectral-domain optical coherence tomography. RESULTS: Over the 34-year period, 74 individuals from 35 families were diagnosed with AED. Sixty individuals from 29 families participated in a follow-up study of whom 59 harbored a CACNA1F mutation and 1 harbored a CABP4 mutation. Among the subjects with a CACNA1F mutation, subnormal visual acuity was present in all, nystagmus was present in 63%, and foveal hypoplasia was observed in 25/43 subjects. Foveal pit volume was significantly reduced as compared to normal (P < 0.0001). Additionally, outer segment length at the fovea was measured in 46 subjects and found to be significantly reduced as compared to normal (P < 0.001). Twenty-nine CACNA1F variations were detected among 34 families in the total cohort, and a novel CABP4 variation was identified in one family. The estimated mean birth prevalence rate was 1 per 22,000 live-born males. CONCLUSIONS: Our data support the viewpoint that AED, iCSNB, and X-linked cone–rod dystrophy 3 are designations that refer to a broad, continuous spectrum of clinical appearances caused in the majority by a variety of mutations in CACNA1F. We argue that the original designation AED should be used for this entity

Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): Exome sequencing of trios, monozygotic twins and tumours

BACKGROUND: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients. METHODS: We sequenced the exomes of seven ROHHAD trios, plus tumours from four of these patients and the unaffected monozygotic (MZ) twin of one (discovery cohort), to identify constitutional and somatic de novo sequence variants. We further analyzed this exome data to search for candidate genes under autosomal dominant and recessive models, and to identify structural variations. Candidate genes were tested by exome or Sanger sequencing in a replication cohort of 28 ROHHAD singletons. RESULTS: The analysis of the trio-based exomes found 13 de novo variants. However, no two patients had de novo variants in the same gene, and additional patient exomes and mutation analysis in the replication cohort did not provide strong genetic evidence to implicate any of these sequence variants in ROHHAD. Somatic comparisons revealed no coding differences between any blood and tumour samples, or between the two discordant MZ twins. Neither autosomal dominant nor recessive analysis yielded candidate genes for ROHHAD, and we did not identify any potentially causative structural variations. CONCLUSIONS: Clinical exome sequencing is highly unlikely to be a useful diagnostic test in patients with true ROHHAD. As ROHHAD has a high risk for fatality if not properly managed, it remains imperative to expand the search for non-exomic genetic risk factors, as well as to investigate other possible mechanisms of disease. In so doing, we will be able to confirm objectively the ROHHAD diagnosis and to contribute to our understanding of obesity, respiratory control, hypothalamic function, and autonomic regulation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-015-0314-x) contains supplementary material, which is available to authorized users

Study of extracellular ribonuclease activity in ustilago hordei

Extracellular ribonuclease activity was detected in culture media of sporidial and mycelial cultures of Ustilago hordei. The RNase activity was maximal at pH 5.0, 6.5 and 8.0. The secretion of the RNase activity was a function of the cell density. Release of pH 4.5 and pH 7.5 activity was coincident. Enrichment of the simple glucose and salts medium delayed the initial secretion of activity. The presence of RNA in the medium did not enhance the amount of activity released. Furthermore, since the presence of RNA in the medium was not required for the release of the RNase activity into the medium, it is suggested the synthesis and secretion is a constitutive function. N-methyl-N'-nitro-N-nitrosoguanidine was used to produce auxotrophic strains. Selection methods for the detection of strains deficient in extracellular RNase activity are discussed.Science, Faculty ofBotany, Department ofGraduat