scholarly journals A novel mutation of ABHD5 gene in a Chanarin Dorfman patient with unusual dermatological findings

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Ali Haydar Eskiocak ◽  
Sara Missaglia ◽  
Laura Moro ◽  
Murat Durdu ◽  
Daniela Tavian
Keyword(s):  
Neutral Lipids ◽  
Novel Mutation ◽  
Autosomal Recessive Disorder ◽  
Skin Lesions ◽  
Clinical Feature ◽  
Nonalcoholic Fatty Liver ◽  
Pityriasis Rubra Pilaris ◽  
Long Time ◽  
History Of

Abstract Background Chanarin Dorfman Syndrome (CDS) is a rare autosomal recessive disorder characterized by the multisytemic accumulation of neutral lipids inside the cytoplasmic lipid droplets. This condition is caused by mutations in the abhydrolase domain containing 5 gene (ABHD5). In CDS the skin involvement is the prevalent and always observed clinical feature, consisting of a non-bullous congenital ichthyosiform erythroderma (NCIE). Moreover, a variable involvement of the liver and neuromuscular system can be also observed. In this report, we aimed to perform the clinical and genetic characterization of a patient affected by CDS with atypical dermatological findings, considering this rare inborn error of neutral lipid metabolism. Methods Genomic DNA samples obtained from patient and his parents were used to perform the sequencing of the ABHD5 exons and their intron/exon boundaries. Bioinformatic analyses were performed to investigate the possible effect of the identified mutation on protein structure. Results Here we present the case of a 29-year-old male patient with CDS, who, for long time, has been misdiagnosed as pityriasis rubra pilaris (PRP). He has a history of increasing hyperlipidemia; hepatomegaly associated with hepatosteatosis was also detected. ABHD5 molecular analysis revealed a novel missense mutation, the c.811G > A (p.G271R). Bioinformatic investigations showed that the variant has a deleterious effect on ABHD5 function, probably causing an incorrect folding of the mutant protein. Conclusions These results highlihts the importance of genetic testing for ABHD5 in unresolved cases of patients presenting unusual skin lesions, that resemble PRP, associated with a history of hyperlipidemia and nonalcoholic fatty liver.

scholarly journals Isolation and Characterization of Akhmeta Virus from Wild-Caught Rodents (Apodemus spp.) in Georgia

2019 ◽  
Vol 93 (24) ◽  
Author(s):  
Jeffrey B. Doty ◽  
Giorgi Maghlakelidze ◽  
Irakli Sikharulidze ◽  
Shin-Lin Tu ◽  
Clint N. Morgan ◽  
...  
Keyword(s):  
Natural History ◽  
Molecular Characterization ◽  
Small Mammals ◽  
Skin Lesions ◽  
Human Populations ◽  
Content Type ◽  
Subsequent Investigation ◽  
Isolation And Characterization ◽  
History Of

ABSTRACT In 2013, a novel orthopoxvirus was detected in skin lesions of two cattle herders from the Kakheti region of Georgia (country); this virus was named Akhmeta virus. Subsequent investigation of these cases revealed that small mammals in the area had serological evidence of orthopoxvirus infections, suggesting their involvement in the maintenance of these viruses in nature. In October 2015, we began a longitudinal study assessing the natural history of orthopoxviruses in Georgia. As part of this effort, we trapped small mammals near Akhmeta (n = 176) and Gudauri (n = 110). Here, we describe the isolation and molecular characterization of Akhmeta virus from lesion material and pooled heart and lung samples collected from five wood mice (Apodemus uralensis and Apodemus flavicollis) in these two locations. The genomes of Akhmeta virus obtained from rodents group into 2 clades: one clade represented by viruses isolated from A. uralensis samples, and one clade represented by viruses isolated from A. flavicollis samples. These genomes also display several presumptive recombination events for which gene truncation and identity have been examined. IMPORTANCE Akhmeta virus is a unique Orthopoxvirus that was described in 2013 from the country of Georgia. This paper presents the first isolation of this virus from small mammal (Rodentia; Apodemus spp.) samples and the molecular characterization of those isolates. The identification of the virus in small mammals is an essential component to understanding the natural history of this virus and its transmission to human populations and could guide public health interventions in Georgia. Akhmeta virus genomes harbor evidence suggestive of recombination with a variety of other orthopoxviruses; this has implications for the evolution of orthopoxviruses, their ability to infect mammalian hosts, and their ability to adapt to novel host species.

Natural History of Sanfilippo Syndrome Type C in Boyacá, Colombia

2016 ◽  
Vol 32 (2) ◽  
pp. 177-183 ◽  
Author(s):  
Harvy Mauricio Velasco ◽  
Yasmin Sanchez ◽  
Angela Milena Martin ◽  
Luis A. Umaña
Keyword(s):  
Natural History ◽  
Novel Mutation ◽  
Autosomal Recessive Disorder ◽  
Sanfilippo Syndrome ◽  
Large Pedigree ◽  
Modifying Factors ◽  
History Of ◽  
Type C ◽  
End Stage ◽  
High Degree

Mucopolysaccharidosis type III, or Sanfilippo syndrome, is an autosomal recessive disorder characterized by impairment in the degradation of Heparan sulfate. Here the authors describe the natural history of 5 related individuals; all associated through a large pedigree which reports a total of 11 affected members, originally from the Boyacá region in Colombia, diagnosed with MPS IIIC who all harbor a novel mutation in HGSNAT. The authors report an unusually high incidence of the disease in this population. The clinical features are similar to previously described patients, although some differences in the degree of severity and end-stage of the disease are seen in this specific group. The authors consider that the high degree of endogamy in this specific population could underlie modifying factors for the severity of presentation in these patients. Future studies might provide more information on the functional effect of this novel mutation, which could define this group as a genetic isolate.

scholarly journals A novel TMPRSS6 mutation that prevents protease auto-activation causes IRIDA

2010 ◽  
Vol 431 (3) ◽  
pp. 363-371 ◽  
Author(s):  
Sandro Altamura ◽  
Flavia D'Alessio ◽  
Barbara Selle ◽  
Martina U. Muckenthaler
Keyword(s):  
Cultured Cells ◽  
Clinical Symptoms ◽  
Novel Mutation ◽  
Functional Characterization ◽  
Transferrin Saturation ◽  
Autosomal Recessive Disorder ◽  
Transmembrane Serine Protease ◽  
Hepcidin Mrna ◽  
Insight Into

IRIDA (iron-refractory iron-deficiency anaemia) is a rare autosomal-recessive disorder hallmarked by hypochromic microcytic anaemia, low transferrin saturation and high levels of the iron-regulated hormone hepcidin. The disease is caused by mutations in the transmembrane serine protease TMPRSS6 (transmembrane protease serine 6) that prevent inactivation of HJV (haemojuvelin), an activator of hepcidin transcription. In the present paper, we describe a patient with IRIDA who carries a novel mutation (Y141C) in the SEA domain of the TMPRSS6 gene. Functional characterization of the TMPRSS6(Y141C) mutant protein in cultured cells showed that it localizes to similar subcellular compartments as wild-type TMPRSS6 and binds HJV, but fails to auto-catalytically activate itself. As a consequence, hepcidin mRNA expression is increased, causing the clinical symptoms observed in this IRIDA patient. The present study provides important mechanistic insight into how TMPRSS6 is activated.

Identification of a novel mutation (C321X) in HJV

Blood ◽  
2004 ◽  
Vol 104 (7) ◽  
pp. 2176-2177 ◽  
Author(s):  
Franklin W. Huang ◽  
Isabel Rubio-Aliaga ◽  
James P. Kushner ◽  
Nancy C. Andrews ◽  
Mark D. Fleming
Keyword(s):  
Family History ◽  
Iron Overload ◽  
Early Onset ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Autosomal Recessive Disorder ◽  
Termination Codon ◽  
Compound Heterozygous ◽  
Juvenile Hemochromatosis ◽  
History Of

Abstract Juvenile hemochromatosis is a rare autosomal recessive disorder characterized by the early onset of severe iron overload. We report the occurrence of compound heterozygous mutations in hemojuvelin (HJV), including a termination codon, in a patient with juvenile hemochromatosis but no family history of iron disorders. (Blood. 2004;104:2176-2177)

Characterization of the Original Christmas Disease Mutation (Cysteine 206 → Serine): From Clinical Recognition to Molecular Pathogenesis

1992 ◽  
Vol 67 (01) ◽  
pp. 063-065 ◽  
Author(s):  
Sherryl A M Taylor ◽  
Jacalyn Duffin ◽  
Cherie Cameron ◽  
Jerome Teitel ◽  
Bernadette Garvey ◽  
...  
Keyword(s):  
Nucleotide Substitution ◽  
Novel Mutation ◽  
Factor Ix ◽  
Causative Mutation ◽  
Coding Region ◽  
Body Of Knowledge ◽  
Polymerase Chain ◽  
Splice Junctions

SummaryChristmas disease was first reported as a distinct clinical entity in two manuscripts published in 1952 (1, 2). The eponym associated with this disorder, is the surname of the first patient examined in detail and reported by Biggs and colleagues in a paper describing the clinical and laboratory features of seven affected individuals (3). This patient has severe factor IX coagulant deficiency (less than 0.01 units/ml) and no detectable circulating factor IX antigen (less than 0.01 units/ml). Coding sequence and splice junctions of the factor IX gene from this patient have been amplified in vitro through the polymerase chain reaction (PCR). One nucleotide substitution was identified at nucleotide 30,070 where a guanine was replaced by a cytosine. This mutation alters the amino acid encoded at position 206 in the factor IX protein from cysteine to serine. The non conservative nature of this substitution, the absence of this change in more than 200 previously sequenced factor IX genes and the fact that the remainder of the coding region of this gene was normal, all provide strong circumstantial evidence in favour of this change being the causative mutation in this patient. The molecular characterization of this novel mutation in the index case of Christmas disease, contributes to the rapidly expanding body of knowledge pertaining to Christmas disease pathogenesis.

BRIDGE BUILDING AS A PROBLEM OF URBAN INFRASTRUCTURE DEVELOPMENT IN THE EUROPEAN NORTH OF RUSSIA IN THE EARLY XX CENTURY

2019 ◽  
Vol 15 (2) ◽  
pp. 125-135
Author(s):  
Tatiana S. Minaeva ◽  
Sergey S. Gulyaev
Keyword(s):  
Urban Infrastructure ◽  
Local Administration ◽  
Infrastructure Development ◽  
European North ◽  
Long Time ◽  
History Of ◽  
Floating Bridge ◽  
Historical Comparative ◽  
Bridge Building ◽  
Xix Century

Introduction. The organization of transport links and the bridge building in cities located on the banks of wide rivers has always been one of the most important tasks of the local administration. The study of the history of bridge building allows not only to trace the process of modernization of different regions of the country, but also to help in solving similar problems of our time. Nevertheless, the history of Russian bridge building is poorly studied. The purpose of the article is to determine the characteristics and features of the organization of bridge building in big cities of the European North of Russia as a way to solve one of the problems of urban infrastructure in the early XX century. Materials and Methods. The sources for this study are the documents of the State archive of the Arkhangelsk region, published documents on the history of Vologda, articles in the local periodicals of the early XX century. The analysis of the studied problem used a systematic approach, the method of economic analysis, historical and historical-comparative methods. Results and Discussion. The building of permanent bridges was a need for the development of Arkhangelsk and Vologda. In Vologda the two wooden bridges were built in the middle of XIX century on city funds and in the future these bridges were repaired or rebuilt. The Arkhangelsk city authorities did not hurry to solve a problem of city infrastructure by own efforts and a long time they used the floating bridge. The lack of experience in the building of large bridges and the desire to save money led to the rapid destruction of the first permanent bridge in Arkhangelsk. Conclusion. The Development of trade and industry in cities of the European North of Russia, such as Arkhangelsk and Vologda, led to the expansion of their territory and the emergence over time, the so-called third parts of the cities. Despite the comparable size of the population of the districts located across the river, the process of connecting them with bridges to the rest of the city went at different rates, which depended on the attitude of the local administration to the problem of urban infrastructure.

A Thorough Theoretical Exploration of Intriguing Characteristics of Cyclo[18]carbon: Geometry, Bonding Nature, Aromaticity, Weak Interaction, Reactivity, Excited States, Vibrations, Molecular Dynamics and Various Molecular Properties

2019 ◽  
Author(s):  
Tian Lu ◽  
Qinxue Chen ◽  
Zeyu Liu
Keyword(s):  
Molecular Dynamics ◽  
Excited States ◽  
Electronic Excitation ◽  
Ring Structure ◽  
Molecular Properties ◽  
Molecular Vibration ◽  
Full Characterization ◽  
Long Time ◽  
Almost All

Although cyclo[18]carbon has been theoretically and experimentally investigated since long time ago, only very recently it was prepared and directly observed by means of STM/AFM in condensed phase (Kaiser et al., <i>Science</i>, <b>365</b>, 1299 (2019)). The unique ring structure and dual 18-center π delocalization feature bring a variety of unusual characteristics and properties to the cyclo[18]carbon, which are quite worth to be explored. In this work, we present an extremely comprehensive and detailed investigation on almost all aspects of the cyclo[18]carbon, including (1) Geometric characteristics (2) Bonding nature (3) Electron delocalization and aromaticity (4) Intermolecular interaction (5) Reactivity (6) Electronic excitation and UV/Vis spectrum (7) Molecular vibration and IR/Raman spectrum (8) Molecular dynamics (9) Response to external field (10) Electron ionization, affinity and accompanied process (11) Various molecular properties. We believe that our full characterization of the cyclo[18]carbon will greatly deepen researchers' understanding of this system, and thereby help them to utilize it in practice and design its various valuable derivatives.

A Thorough Theoretical Exploration of Intriguing Characteristics of Cyclo[18]carbon: Geometry, Bonding Nature, Aromaticity, Weak Interaction, Reactivity, Excited States, Vibrations, Molecular Dynamics and Various Molecular Properties

2019 ◽  
Author(s):  
Tian Lu ◽  
Qinxue Chen ◽  
Zeyu Liu
Keyword(s):  
Molecular Dynamics ◽  
Excited States ◽  
Electronic Excitation ◽  
Ring Structure ◽  
Molecular Properties ◽  
Molecular Vibration ◽  
Full Characterization ◽  
Long Time ◽  
Almost All

Although cyclo[18]carbon has been theoretically and experimentally investigated since long time ago, only very recently it was prepared and directly observed by means of STM/AFM in condensed phase (Kaiser et al., <i>Science</i>, <b>365</b>, 1299 (2019)). The unique ring structure and dual 18-center π delocalization feature bring a variety of unusual characteristics and properties to the cyclo[18]carbon, which are quite worth to be explored. In this work, we present an extremely comprehensive and detailed investigation on almost all aspects of the cyclo[18]carbon, including (1) Geometric characteristics (2) Bonding nature (3) Electron delocalization and aromaticity (4) Intermolecular interaction (5) Reactivity (6) Electronic excitation and UV/Vis spectrum (7) Molecular vibration and IR/Raman spectrum (8) Molecular dynamics (9) Response to external field (10) Electron ionization, affinity and accompanied process (11) Various molecular properties. We believe that our full characterization of the cyclo[18]carbon will greatly deepen researchers' understanding of this system, and thereby help them to utilize it in practice and design its various valuable derivatives.

A Rare Case of Spinal Leprosy Mimicking Spinal Tuberculosis

2019 ◽  
pp. 33
Author(s):  
K Thuraikumar ◽  
V Naveen ◽  
Mustaqim A ◽  
Arieff AA ◽  
K Shri ◽  
...  
Keyword(s):  
Back Pain ◽  
Soft Tissue ◽  
Histopathological Examination ◽  
Posterior Instrumentation ◽  
Spinal Tuberculosis ◽  
Previous History ◽  
Skin Lesions ◽  
Titanium Implants ◽  
Paravertebral Abscess ◽  
History Of

Introduction: Spinal tuberculosis is the most common manifestation of extrapulmonar y tuberculosis. A combination of leprosy and tuberculosis is a rare entity.Case report: A 44-year-old male patient working as a laborer presented to our hospital with complaints of severe back pain and swelling over the back, difficulty in walking, associated with constitutional symptoms. On admission, he was febrile and had leukocytosis. Initial spine X-ray showed end plate destruction and increase in soft tissue shadow at the level of T8-T9. CT spine revealed thoracic paravertebral collection extending from T7 to T9 levels, suggest ive of tuberculous spondylitis with cold abscess. Patient refused a transpedicular biopsy and was started on anti-tubercular therapy. Two weeks after commencement of treatment, he developed worsening back pain and weakness of the lower extremities. MRI spine showed a paravertebral abscess and posterior soft tissue edema involving level of T7 to T11. Patient underwent a posterior decompression, debridement and posterior instrumentation. He was discharged well, there was improvement of his lower limb power. Upon clinic review, he complained of multiple hyperpigmented, painless, nonpruritic skin lesions over the trunk and back. No previous history of eczema, psoriasis and Tinea corporis. Given the history of allergy, initial impression was hypersensitivity reaction towards the titanium implants, and he was started on anti-histamines. However, there was no improvements seen. Histopathological examination of skin lesions revealed presence of granuloma within the dermis layer, composed of epitheloid, histiocytes, lymphocytes and plasma cells. Wade-Fite stain for Mycobacterium leprae is positive. Slit skin smear shows multibacillary leprosy. Patient was started on multidrug therapy (rifampicin, clofazimine and dapsone) for 1 year. He has recovered well.International Journal of Human and Health Sciences Supplementary Issue: 2019 Page: 33

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