Search

Background Hereditary Multiple Exostoses (HME), also known as Multiple Osteochondromas (MO) is a rare genetic disorder characterized by multiple benign cartilaginous bone tumors, which are caused by mutations in the genes for exostosin glycosyltransferase 1 (EXT1) and exostosin glycosyltransferase 2 (EXT2). The genetic defects have not been studied in the Saudi patients. Aim of study We investigated mutation spectrum of EXT1 and EXT2 in 22 patients from 17 unrelated families. Methods Genomic DNA was extracted from peripheral leucocytes. The coding regions and intron–exon boundaries of both EXT1 and EXT2 genes were screened for mutations by PCR-sequencing analysis. Gross deletions were analyzed by MLPA analysis. Results EXT1 mutations were detected in 6 families (35%) and 3 were novel mutations: c.739G > T (p. E247*), c.1319delG (p.R440Lfs*4), and c.1786delA (p.S596Afs*25). EXT2 mutations were detected in 7 families (41%) and 3 were novel mutations: c.541delG (p.D181Ifs*89), c.583delG (p.G195Vfs*75), and a gross deletion of approximately 10 kb including promoter and exon 1. Five patients from different families had no family history and carried de novo mutations (29%, 5/17). No EXT1 and EXT2 mutations were found in the remaining four families. In total, EXT1 and EXT2 mutations were found in 77% (13/17) of Saudi HME patients. Conclusion EXT1 and EXT2 mutations contribute significantly to the pathogenesis of HME in the Saudi population. In contrast to high mutation rate in EXT 1 (65%) and low mutation rate in EXT2 (25%) in other populations, the frequency of EXT2 mutations are much higher (41%) and comparable to that of EXT1 among Saudi patients. De novo mutations are also common and the six novel EXT1/EXT2 mutations further expands the mutation spectrum of HME.

Hereditary sensory autonomic neuropathy type IV (HSAN-IV) is a rare autosomal recessive disorder that usually begins in infancy and is characterized by anhidrosis, insensitivity to noxious stimuli leading to self-mutilating behavior, and intellectual disability. HSAN-IV is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene, NTRK1, encoding the high-affinity receptor of nerve growth factor (NGF) which maps to chromosome 1q21-q22. Patients with HSAN-IV lack all NGF-dependent neurons, the primary afferents and sympathetic postganglionic neurons leading to lack of pain sensation and the presence of anhidrosis, respectively. Herein, we report nine patients from nine unrelated families with HSAN-IV due to various mutations in NTRK1, five of which are novel. These are three missense and two nonsense mutations distributed in various domains of NTRK1 involved in binding of NGF. The affected patients had variable intellectual deficits, and some had delayed diagnosis of HSAN-IV. In addition to being the first report of HSAN-IV from the Arabian Peninsula, this report expands the mutational spectrum of patients with NTRK1 mutations and provides further insights for molecular and clinical diagnosis.

Stereochemistry plays a significant role in structure–activity relationships of messenger chemicals. The ability to distinguish between enantiomers and geometric isomers, however, may be limited to certain stereoisomeric substances, depending on the receiver. In this study, we assessed the preference of the peripheral olfactometry system of Western Flower Thrips, F. occidentalis towards ubiquitously expressed host compounds, with a goal of establishing whether particular stereoisomers enhance host odour recognition. We demonstrate that the peripheral olfactory system of a highly polyphagous thysanopteran insect has evolved to become highly sensitive to a type of green leaf volatile, which is highly ubiquitous in the plant kingdom. We show that there is a significantly greater antennal response to the cis isomer, more so than the isomerisation by-product trans-3-hexen-1-ol. We demonstrate that the antennae of a highly polyphagous insect are capable of detecting common plant secondary metabolites in both enantiomeric forms. Electronic supplementary material The online version of this article (doi:10.1007/s00049-014-0173-2) contains supplementary material, which is available to authorized users.

Background Osteogenesis imperfecta (OI) is an hereditary bone disease in which increased bone fragility leads to frequent fractures and other complications, usually in an autosomal dominant fashion. An expanding list of genes that encode proteins related to collagen metabolism are now recognised as important causes of autosomal recessive (AR) OI. Our aim was to study the contribution of known genes to AR OI in order to identify novel loci in mutation-negative cases. Methods We enrolled multiplex consanguineous families and simplex cases (also consanguineous) in which mutations in COL1A1 and COL1A2 had been excluded. We used autozygome guided mutation analysis of AR OI (AR OI) genes followed by exome sequencing when such analysis failed to identify the causative mutation. Results Two simplex and 11 multiplex families were enrolled, encompassing 27 cases. In three multiplex families, autozygosity and linkage analysis revealed a novel recessive OI locus on chromosome 9q31.1-31.3, and a novel truncating deletion of exon 4 of TMEM38B was identified within that interval. In addition, gonadal or gonadal/somatic mosaic mutations in COL1A1 or COL1A2 and homozygous mutations in recently described AR OI genes were identified in all remaining families. Conclusions TMEM38B is a novel candidate gene for AR OI. Future studies are needed to explore fully the contribution of this gene to AR OI in other populations.

Bruck syndrome (BS) is an autosomal recessive syndromic form of osteogenesis imperfecta (OI) that is characterized by the additional presence of pterygium formation. We have recently shown that FKBP10 previously reported as a novel autosomal recessive OI gene also defines a novel Bruck syndrome locus (BKS3). In this manuscript, we extend our analysis to describe a mutation previously described in isolated OI patients and show that it results in BS phenotype in a Saudi family. More interestingly, we describe a novel FKBP10 mutation that results in isolated OI as well as BS phenotype in the same family. These results, combined with recently published work, confirm that FKBP10 is a bonafide BS locus and lay the foundation for future research into modifiers that underlie the phenotypic heterogeneity of FKBP10 mutations.

Monitoring of pest populations is an essential component of integrated pest management. An early warning system helps growers decide when best to take control measures, or when to alter them, should a control method prove inadequate. Studies have shown that adding chemical attractants to sticky cards can increase trap catch of western flower thrips, Frankliniella occidentalis, a global pest of agriculture and horticulture, giving more accurate accounts of population size and dynamics, thus leading to more efficient monitoring. We identify a novel semiochemical to the species, (S)-(−)-verbenone, showing that addition of this compound to sticky traps significantly increased F. occidentalis catch in two geographically distinct populations, infesting two unrelated crops of global economic importance. We validate through field trials that (S)-(−)-verbenone is highly attractive to F.occidentalis and can be used with blue sticky traps to enhance trap catch, leading to better estimations of pest population densities. The compound may be used in other control methods against F.occidentalis such as lure and kill, mass trapping and push-pull. Electronic supplementary material The online version of this article (doi:10.1186/s40064-015-0864-3) contains supplementary material, which is available to authorized users.

Pollinophagy is widely documented in the order Thysanoptera, with representative individuals from six of the nine divergent families known to feed on pollen. Various pollens of the genus Pinus increase the development time, fecundity, longevity, and settling preference of Western Flower Thrips (WFT), Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae). Certain species of flower thrips discriminate among pollen types, but no studies have elucidated the olfactory cues that play a role in their pollen preferences. In this study, the volatile organic compounds emitted by pollens of the genus Pinus were elucidated. Various chemicals from pollen headspace elicited electrophysiological responses from WFT antennae. The compound (S)-(-)-verbenone, identified in pollen headspace, attracted WFT in a 4-arm olfactometer. This compound has potential for use in integrated pest management programs against the pest. We present the hypothesis that this polyphagous insect may have retained ancestral ‘relict’ olfactory receptors through the course of evolution, to explain this attraction to pine pollen. This attraction has allowed the insect to find and exploit an unusual nutrient source that significantly increases its fitness. The study demonstrates how fossil record analysis and subsequent evolutionary knowledge can aid in explaining possibilities as to why some insects sense and respond to chemicals that would otherwise seem peculiar to their ecology, allowing insight into the evolutionary forces that may shape insect olfactory systems over time. Electronic supplementary material The online version of this article (doi:10.1007/s10886-014-0450-0) contains supplementary material, which is available to authorized users.

(American Journal of Human Genetics 87, 306–307)We mistakenly designated the mutation in FKBP10 (NM_ 021939.3) in our two patients as c.1023insGGAGAATT and p.T342GfsX367. The proper designation is c.1016_1023dup and p.Thr342GlyfsX26. This error appears both in the text and in Figure 1Figure 1E , in which we also showed the two mutations mistakenly described by Alanay et al as p.Gly107_Leu117del (the correct designation is p.Met107_Leu117del) and p.Gly278ArgfsX295 (the correct designation is p.Gly278ArgfsX95).1xMutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Alanay, Y., Avaygan, H., Camacho, N., Utine, G.E., Boduroglu, K., Aktas, D., Alikasifoglu, M., Tuncbilek, E., Orhan, D., Bakar, F.T. et al. Am. J. Hum. Genet. 2010; 86: 551–559Abstract | Full Text | Full Text PDF | PubMed | Scopus (133)See all References1 A revised version of Figure 1Figure 1 with the three mutations properly named is shown below. Additionally, “protrusion” now reads “protrusio,” and “inserted” has been replaced with “duplicated” in the legend. The authors regret this oversight and appreciate the opportunity to amend the record.Figure 1A Novel FKBP10 Mutation in Two Siblings with Bruck Syndrome(A) Clinical photographs of the index patient and (B) his brother showing fixed flexion deformity of the elbows. (C) Note the severe flexion deformity of the knees in the index patient; the ankles are less severely involved. (D) Thoracolumar spine X-ray showing scoliosis and osteopenia. Severe protrusio acetabuli and intrmedullary rod fixation of the right femur fracture can also be seen. (E) Schematic representation of FKBP65 with the location of mutations indicated by arrows. Our mutation is boxed and shown next to the sequence chromatogram; the duplicated 8 bp are indicated by a red line.View Large Image | View Hi-Res Image | Download PowerPoint Slide