Biallelic loss-of-function (LoF) variants in CENPF gene are responsible for Stromme syndrome, a condition presenting with intestinal atresia, anterior ocular chamber anomalies, and microcephaly.... Show moreBiallelic loss-of-function (LoF) variants in CENPF gene are responsible for Stromme syndrome, a condition presenting with intestinal atresia, anterior ocular chamber anomalies, and microcephaly. Through an international collaboration, four individuals (three males and one female) carrying CENPF biallelic variants, including two missense variants in homozygous state and four LoF variants, were identified by exome sequencing. All individuals had variable degree of developmental delay/intellectual disability and microcephaly (ranging from -2.9 SDS to -5.6 SDS) and a recognizable pattern of dysmorphic facial features including inverted-V shaped interrupted eyebrows, epicanthal fold, depressed nasal bridge, and pointed chin. Although one of the cases had duodenal atresia, all four individuals did not have the combination of internal organ malformations of Stromme syndrome (intestinal atresia and anterior eye segment abnormalities). Immunofluorescence analysis on skin fibroblasts on one of the four cases with the antibody for ARL13B that decorates primary cilia revealed shorter primary cilia that are consistent with a ciliary defect. This case-series of individuals with biallelic CENPF variants suggests the spectrum of clinical manifestations of the disorder that may be related to CENPF variants is broad and can include phenotypes lacking the cardinal features of Stromme syndrome. Show less
Damme, M. van; Clarisse, L.; Franco, B.; Sutton, M.A.; Erisman, J.W.; Wichink Kruit, R.; ... ; Coheur, P.F. 2020
Excess atmospheric ammonia (NH3) leads to deleterious effects on biodiversity, ecosystems, air quality and health, and it is therefore essential to monitor its budget and temporal evolution.... Show moreExcess atmospheric ammonia (NH3) leads to deleterious effects on biodiversity, ecosystems, air quality and health, and it is therefore essential to monitor its budget and temporal evolution. Hyperspectral infrared satellite sounders provide daily NH3 observations at global scale for over a decade. Here we use the version 3 of the Infrared Atmospheric Sounding Interferometer (IASI) NH3 dataset to derive global, regional and national trends from 2008 to 2018. We find a worldwide increase of 12.8 ± 1.3 % over this 11-year period, driven by large increases in east Asia (5.80 ± 0.61 % increase per year), western and central Africa (2.58 ± 0.23 %.yr−1), North America (2.40 ± 0.45 %.yr−1) and western and southern Europe (1.90 ± 0.43 %.yr−1). These are also seen in the Indo-Gangetic Plain, while the southwestern part of India exhibits decreasing trends. Reported national trends are analyzed in the light of changing anthropogenic and pyrogenic NH3 emissions, meteorological conditions and the impact of sulfur and nitrogen oxides emissions, which alter the atmospheric lifetime of NH3. We end with a short case study dedicated to the Netherlands and the "Dutch Nitrogen crisis" of 2019. Show less
We present a retrieval method for ammonia (NH3) total columns from ground-based Fourier transform infrared (FTIR) observations. Observations from Bremen (53.10 degrees N, 8.85 degrees E), Lauder ... Show moreWe present a retrieval method for ammonia (NH3) total columns from ground-based Fourier transform infrared (FTIR) observations. Observations from Bremen (53.10 degrees N, 8.85 degrees E), Lauder (45.04 degrees S, 169.68 degrees E), Reunion (20.9 degrees S, 55.50 degrees E) and Jungfraujoch (46.55 degrees N, 7.98 degrees E) were used to illustrate the capabilities of the method. NH3 mean total columns ranging 3 orders of magnitude were obtained, with higher values at Bremen (mean of 13 : 47 x 10(15) molecules cm(-2)) and lower values at Jungfraujoch (mean of 0 : 18 x 10(15) molecules cm(-2)). In conditions with high surface concentrations of ammonia, as in Bremen, it is possible to retrieve information on the vertical gradient, as two layers can be distinguished. The retrieval there is most sensitive to ammonia in the planetary boundary layer, where the trace gas concentration is highest. For conditions with low concentrations, only the total column can be retrieved. Combining the systematic and random errors we have a mean total error of 26% for all spectra measured at Bremen (number of spectra (N) = 554), 30% for all spectra from Lauder (N = 2412), 25% for spectra from Reunion (N = 1262) and 34% for spectra measured at Jungfraujoch (N = 2702). The error is dominated by the systematic uncertainties in the spectroscopy parameters. Station-specific seasonal cycles were found to be consistent with known seasonal cycles of the dominant ammonia sources in the station surroundings. The developed retrieval methodology from FTIR instruments provides a new way of obtaining highly time-resolved measurements of ammonia burdens. FTIR-NH3 observations will be useful for understanding the dynamics of ammonia concentrations in the atmosphere and for satellite and model validation. It will also provide additional information to constrain the global ammonia budget. Show less
Sun, Y.; Almomani, R.; Aten, E.; Celli, J.; Heijden, J. van der; Venselaar, H.; ... ; Breuning, M.H. 2010
Terminal osseous dysplasia (TOO) is an X-linked dominant male-lethal disease characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibroma with... Show moreTerminal osseous dysplasia (TOO) is an X-linked dominant male-lethal disease characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibroma with onset in female infancy. After performing X-exome capture and sequencing, we identified a mutation at the last nucleotide of exon 31 of the FLNA gene as the most likely cause of the disease. The variant c.5217G>A was found in six unrelated cases (three families and three sporadic cases) and was not found in 400 control X chromosomes, pilot data from the 1000 Genomes Project, or the FLNA gene variant database. In the families, the variant segregated with the disease, and it was transmitted four times from a mildly affected mother to a more seriously affected daughter. We show that, because of nonrandom X chromosome inactivation, the mutant allele was not expressed in patient fibroblasts. RNA expression of the mutant allele was detected only in cultured fibroma cells obtained from 15-year-old surgically removed material. The variant activates a cryptic splice site, removing the last 48 nucleotides from exon 31. At the protein level, this results in a loss of 16 amino acids (p.Val1724_Thr1739del), predicted to remove a sequence at the surface of filamin repeat 15. Our data show that TOD is caused by this single recurrent mutation in the FLNA gene. Show less
