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Background: Microduplications are a rare cause of disease in X-linked neurodevelopmental disorders but likely have been under reported due challenges in detection and interpretation., Methods: We performed exome sequencing and subsequent microarray analysis in two families with a neurodevelopmental disorder., Results: Here, we report on two families each with unique inherited microduplications at Xp21.2 and Xq13.1, respectively. In the first family, a 562.8-kb duplication at Xq13.1 covering DLG3, TEX11, SLC7A3, GDPD2, and part KIF4A was identified in a boy whose phenotype was characterized by delayed speech development, mild intellectual disability (ID), mild dysmorphic facial features, a heart defect, and neuropsychiatric symptoms. By interrogating all reported Xq13.1 duplications in individuals affected with a neurodevelopmental disorder, we provide evidence that this genomic region and particularly DLG3 might be sensitive to an increased dosage. In the second family with four affected males, we found a noncontinuous 223- and 204-kb duplication at Xp21.2, of which the first duplication covers exon 6 of IL1RAPL1. The phenotype of the male patients was characterized by delayed speech development, mild to moderate ID, strabismus, and neurobehavioral symptoms. The carrier daughter and her mother had learning difficulties. IL1RAPL1 shows nonrecurrent causal structural variation and is located at a common fragile site (FRAXC), prone to re-arrangement., Conclusion: In conclusion, we show that comprehensive clinical and genetic examination of microduplications on the X-chromosome can be helpful in undiagnosed cases of neurodevelopmental disease., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Pectins, complex plant-derived polysaccharides, are novel candidates for biomaterial nanocoatings. Pectic rhamnogalacturonan-I regions (RG-I) can be enzymatically treated to so-called modified hairy regions (MHR). We surveyed the growth and differentiation of murine preosteoblastic MC3T3-E1 cells on Petri dishes coated with RG-Is from native or genetically engineered potato tubers. Uncoated tissue culture polystyrene (TCPS) and aminated (AMI) dishes served as controls. MHRPTR_GAL sample was depleted of galactose (9 mol % galactose; 23 mol % arabinose) and MHRPTR_ARA of arabinose (61 mol % galactose; 6 mol % arabinose). Wild-type (modified hairy region from potato pectin (MHRP)_WT) fragment contained default amounts (58 mol % galactose; 13 mol % arabinose) of both sugars. Focal adhesions (FAs) indicating cellular attachment were quantified. Reverse transcriptase polymerase chain reaction (RT-PCR) of alkaline phosphatase and osteocalcin genes indicating osteoblastic differentiation was performed along with staining the produced calcium with tetracycline as an indicator of osteoblastic differentiation. Osteoblasts proliferated on all the samples to some extent. The control surfaces performed better than any of the pectin samples, of which the MHRP_WT seemed to function best. FA length was greater on MHRPTR_GAL than on other pectin samples, otherwise the mutants did not significantly deviate. RT-PCR results indicate that differences between the samples at the gene expression level might be even subtler. However, tetracycline-stained calcium-containing mineral was detected merely only on uncoated TCPS. These results indicate the possibility to affect bone cell growth with in vivo-modified pectin fragments, consecutively providing information on the significance of certain monosaccharides on the biocompatibility of these polysaccharides., (Copyright © 2011 Wiley Periodicals, Inc.)

Multiform coated titanium implants are widely used in orthopedic and dental surgery. In this study, we have investigated the reactivity of pectin-coated titanium samples implanted under the latissimus dorsi-muscle fascia of rats. Samples were coated with two enzyme treated apple pectins; modified hairy regions (MHR-A and MHR-B) that differed in chemical structure. Aminated (AMI) and uncoated titanium (Ti) served as controls. The thicknesses of the peri-implant fibrous tissue capsules formed 1 or 3 weeks after implantation were measured as indicative of possible inflammatory reactions toward the biomaterials. After 1 week, the MHR-B implant was surrounded by a thicker fibrous capsule (42.9 microm) than any of the other sample types: MHR-A (33.2 microm), AMI (32.5 microm), and Ti (32.3 microm), the last one being the only statistically significant difference. After 3 weeks, however, this difference disappeared; the capsule thicknesses around MHR-B and Ti implants had decreased to the values found for AMI and MHR-A. Additionally, the capsule formation represents merely a stromal rather than an inflammatory reaction, as indicated by the absence of activated macrophages or foreign body giant cells in the capsules. These results indicate for the first time the in vivo tolerability of covalently linked pectins, and suggest the feasibility of pectin-coated bone and dental implants for clinical use., ((c) 2009 Wiley Periodicals, Inc.)