No abstract

We document three new patients with fibular agenesis, tibial campomelia, and oligosyndactyly (FATCO). Two of these individuals had tetramelic manifestations while the third had bilateral abnormalities of the lower limbs. These patients and others reported as FATCO seem to belong to the phenotype "fibular aplasia with ectrodactyly." Genetic screening for CNVs and mutations in the TP63 and WNT10B genes did not show any genetic abnormalities. ©

In 1999, based on a single family, spondyloepimetaphyseal dysplasia (SEMD) with mental retardation (MR) was described as a novel syndrome with probably X-linked recessive inheritance and unknown molecular defect (MIM 300232). Our purpose was to search for the causative defect in the originally described family and in an independently ascertained second family. All patients had slowly progressive neurodegeneration with central and peripheral involvement and identical skeletal dysplasia. Whole exome sequencing performed in two subjects showed a single plausible candidate - the p.Asp237Gly variant in AIFM1 (chr. Xq26.1). The p.Asp237Gly segregated with disease as indicated by linkage analysis [maximum logarithm of odds score (LOD) score at theta 0 for the two families was 3.359]. This variant had not been previously reported and it was predicted to be pathogenic by Polyphen2, SIFT, MutationTaster and Mutation Assessor. AIFM1 encodes mitochondria associated apoptosis-inducing factor. The AIFM1 gene has been linked with COXPD6 encephalomyopathy (MIM 300816), Cowchock syndrome (MIM 310490) and X-linked deafness with neuropathy (DFNX5, MIM 300614), none of which are similar to SEMD-MR. Our results place SEMD as the third instance of a skeletal phenotype associated with a mitochondrial disease (the others being EVEN-PLUS syndrome caused by mutations of HSPA9 and CODAS syndrome due to LONP1 mutations).

Sclerosteosis and Van Buchem disease are related recessive sclerosing bone dysplasias caused by alterations in the SOST gene. We tested the hypothesis that craniodiaphyseal dysplasia (CDD) (MIM 122860), an extremely rare sclerosing bone dysplasia resulting facial distortion referred to as ''leontiasis ossea'', could also be caused by SOST mutations. We discovered mutations c.61G[A (Val21Met) and c.61G[T (Val21Leu) two children with CDD. As these mutations are located in the secretion signal of the SOST gene, we tested their effect on secretion by transfecting the mutant constructs into 293E cells. Intriguingly, these mutations greatly reduced the secretion of SOST. We conclude that CDD, the most severe form of sclerotic bone disease, is part of a spectrum of disease caused by mutations in SOST. Unlike the other SOST-related conditions, sclerosteosis and Van Buchem disease that are inherited as recessive traits seem to be caused by a dominant negative mechanism.

With increasing use of CT in children and a lack of use of appropriateness criteria, there is a strong need to implement guidelines to avoid unnecessary radiation doses to children.

Summary:The new polymer gel dosimeter, based on the modification of the VIPAR gel composition, is described for the purpose of radiation dose distribution measurement in radiotherapy. It features increased concentration of the two VIPAR substrates: N-vinylpyrrolidone (8%) and gelatine (7.5%) (N,N 0 -methylenebisacrylamide was maintained at 4%), and the addition of copper sulphate (0.0008%) and ascorbic acid (0.007%) in order to facilitate the preparation through elimination of the need for deoxygenation of the gel. Following the exposure to ionizing radiation, polymerisation and cross-linking of the new gel monomers occurs retaining the spatial distribution of absorbed dose and causing opacity of the gel. Quantitative parameters of the new gel dose response were studied using magnetic resonance imaging to relate polymerisation induced physicochemical changes of the gel to dose. The dose threshold is found significantly lower than that of the original VIPAR gel. The linear part of measured spin-spin relaxation rate R 2 (D) ( ¼ 1/T 2 (D)) reaches up to 35 Gy. Its slope and an intercept are slightly higher relative to the original VIPAR. The efficiency of the new polymer gel-magnetic resonance imaging dosimeter was also tested for dose verification of a 3D dose distribution planned by a commercially available treatment planning software (Eclipse External Beam v.6.5) and delivered by a 6 MV medical linear accelerator. The new polymer gel is proposed to be called, VIPAR nd (after VIPAR-normoxic-double).

We report two patients with Robinow syndrome, review the published literature and stress the importance and limitations of radiographic examination in the diagnosis of this disorder, which shows extreme clinical and radiographic variability. The radiographic differential diagnosis of Robinow syndrome is discussed.

For an 80-fold purified preparation of human intestinal diamine oxidase the optimum conditions of incubation, the substrate and the inhibitor specificity were tested. Putrescine was the most favoured substrate but N tau-methylhistamine and 2-methylhistamine were metabolized at optimum conditions with nearly the same velocity. Histamine reached about 50% of the reaction velocity of putrescine. Aminoguanidine and semicarbazide inhibited the human intestinal enzyme like a classical diamine oxidase. However, a distinct inhibition of human intestinal and pea seedling diamine oxidase was observed in presence of beta-aminopropionitrile (weak inhibition of the human enzyme, strong inhibition of pea seedling diamine oxidase) and burimamide (strong inhibition of human intestinal enzyme, nearly no influence on pea seedling diamine oxidase). It is proposed to differentiate on the basis of functional considerations diamine oxidases with more histamine detoxicating activities from those being more involved in regulating polyamine levels in growing tissues.