Exposing the human nude phenotype [4]

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Maternal Germline Mosaicism in Dominant Dystrophic Epidermolysis Bullosa

3 páginas, 1 figura.Here, we report a family with one child affected by mild DEB. At birth, blistering and denuded areas were present together with the syndactyly of the second and third toes. By the age of 11 mo, blistering was significantly reduced but the blisters healed with hyperpigmented and hypopigmented scars and milia. Both parents and an older sibling were clinically unaffected, and there was no family history of consanguinity or of a blistering disorder or skin fragility.Peer reviewe

Identification of novel type VII collagen gene mutations resulting in severe recessive dystrophic epidermolysis bullosa

5 páginas, 2 figuras.In this work, we studied the proband in a small nuclear family of Chinese and Dutch/German descent and identified two novel mutations in the type VII collagen gene leading to recessive dystrophic epidermolysis bullosa, Hallopeau–Siemens variant (HS-RDEB). The maternal mutation is a single base pair deletion of a cytosine nucleotide in exon 26, designated 3472delC, resulting in a frameshift and a premature termination codon (PTC) within the same exon, 7 bp downstream of the site of the mutation. The paternal mutation is a G→A transition located at the 5′ donor splice site within intron 51, designated IVS51 + 1G→A. This mutation leads to the activation of a cryptic splice site, 32 bp downstream of the mutation site and to subsequent aberrant out-of-frame splicing, resulting in two alternative mRNA transcripts and a downstream PTC. To our knowledge, these two mutations have not been previously reported. These findings extend the body of evidence for compound heterozygous mutations leading to HS-RDEB and provide the basis for prenatal diagnosis in this family.This study was supported by NIH AR43602 (A.M.C), R03 AR47184 (P.B.C) and T32 AR07605 (M.M).Peer reviewe

Моделирование магнитного поля трехвиткового безжелезного электромагнита ускорителя электронов

Выпускная квалификационная работа выполнена на 91 листе машинописного текста, содержит 14 рисунков, 24 таблица, 24 источника, 1 Приложение. Ключевые слова: модель, моделирование, ускорение, бетатрон, COMSOL, метод конечных элементов, магнитная индукция, частицы. Объект исследования ¬– взаимодействие электронных пучков с электромагнитными полями: вихревыми ускоряющими и фокусирующими (слабая фокусировка). Целью работы является выбор максимального рабочего пространства для электронов, устойчиво двигающихся по замкнутым орбитам посредством выбора кривизны медных колец, их диаметра, и величины токов, протекающих по ним. В ходе выполнения работы проводилась разработка математической модели безжелезного компактного ускорителя электронов и моделирование его электромагнитного поля в пакете програмFinal qualifying work carried out by 91 sheet of typewritten text, contains 14 figures, 24 table, 24 sources, Appendix 1. Keywords: model, simulation, acceleration, the betatron, of COMSOL, finite element method, magnetic flux density, particle. Object of research ¬- the interaction of electron beams with electromagnetic fields: eddy accelerating and focusing (weak focusing). The aim is to select the maximum working space for the electrons, moving steadily along closed orbits by selecting the curvature of copper rings, their diameter, and the magnitude of the currents flowing through them. In the course of the work carried out to develop a mathematical model of heavy metal-free compact electron accelerator and its simulation of the electromagnetic field in the package COMSOL Multiphysics

A novel missense mutation in the COL7A1 gene underlies epidermolysis bullosa pruriginosa

13 páginas, 2 figuras.Epidermolysis bullosa (EB) pruriginosa is a subtype of dominant dystrophic EB (DDEB), characterized by severe pruritus and blistering localized to the extensor surface of the extremities. EB pruriginosa exhibits extensive clinical heterogeneity with variable expression and delayed age of onset. Mutations in the COL7A1 gene, especially in glycine residues within Gly-X-Y repeats, have been shown to cause this form of DDEB. Here, we report a novel COL7A1 mutation in a Taiwanese pedigree with EB pruriginosa. Using PCR and direct sequence analysis we have identified a G→T transversion at nucleotide 7097 in exon 92 of COL7A1, converting a glycine residue to valine (G2366V). The mutation resides within a consecutive, uninterrupted stretch of 17 Gly-X-Y residues in the triple-helical domain of type VII collagen. Interestingly, an affected member of this family also displayed elevated IgE levels, previously reported in some patients with this disorder. Our finding further implicates COL7A1 mutation in the pathogenesis of EB pruriginosa and underscores the heterogeneous clinical symptoms of glycine mutations in DDEB.This work was supported in part by NIH R01 AR43602 (A.M.C) and R03 AR47184 (P.B.C). G.S.C. is a fellow of Howard Hughes Medical Institute-Medical Student Training Fellowship.Peer reviewe

Germline fumarate hydratase mutations and evidence for a founder mutation underlying multiple cutaneous and uterine leiomyomata

23 páginas, 3 figuras, 1 tabla.Multiple cutaneous and uterine leiomyomata syndrome (MCL) is an autosomal dominant disease characterized by the presence of concurrent benign tumors of smooth muscle origin (leiomyoma) in the skin and uterus of affected females, and in the skin of affected males. MCL can also be associated with type II papillary renal cell cancer (HLRCC). The genetic locus for MCL and HLRCC was recently mapped to chromosome 1q42.3-43 and subsequently, dominantly inherited mutations in the fumarate hydratase gene (FH) were identified. Importantly, analysis of the FH gene in tumors of MCL patients revealed a second mutation inactivating the wild-type allele in some tumors. Based on these findings, it has been suggested that FH may function as a tumor suppressor gene in MCL. Here, we report the analysis of the FH gene in a group of 11 MCL families, with the identification of 8 different mutations accounting for the disease in all families. One of the mutations, 905-1G>A, has been identified in 4 families of Iranian origin. The analysis of highly polymorphic markers in the vicinity of the FH gene showed a shared haplotype in these 4 families, suggesting that 905-1G>A represents a founder mutation. Collectively, identification of 5 novel and 3 recurrent mutations further supports the role of FH in the pathogenesis of MCL.Supported in part by the Skin Disease Research Center, Department of Dermatology, Columbia University (P30 AR44535), a National Institutes of Health research grant (K01-HG0005501), and a research grant from the Women's Health Program, supported by HWZOA. G. S. C. is a fellow of Howard Hughes Medical Institute-Medical Student Training Fellowship.Peer reviewe