scholarly journals Evidence for non-Mendelian inheritance in spastic paraplegia 7

2020 ◽  
Author(s):  
Mehrdad A Estiar ◽  
Eric Yu ◽  
Ikhlass Haj Salem ◽  
Jay P Ross ◽  
Kheireddin Mufti ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Mendelian Inheritance ◽  
Spinocerebellar Ataxia Type ◽  
Fisher Exact Test ◽  
Spastic Paraplegia ◽  
Motor Neuron Diseases ◽  
Exact Test ◽  
Digenic Inheritance ◽  
Complex Inheritance ◽  
Index Cases

Hereditary spastic paraplegia is a group of rare motor neuron diseases considered to be inherited in a classical monogenic Mendelian manner. Although the typical inheritance of spastic paraplegia type 7 is autosomal recessive, several reports have suggested that SPG7 variants may also cause autosomal dominant HSP. We aimed to conduct an exome-wide genetic analysis on a large Canadian cohort of hereditary spastic paraplegia patients and controls to examine the association of SPG7 and hereditary spastic paraplegia. In total, 585 hereditary spastic paraplegia patients from 372 families and 1,175 controls, including 580 unrelated individuals, were analyzed for the presence of SPG7 variants. Whole exome sequencing was performed on 400 hereditary spastic paraplegia patients (291 index cases) and all 1,175 controls. After excluding 38 biallelic hereditary spastic paraplegia type 7 patients, the frequency of heterozygous pathogenic/likely pathogenic SPG7 variant carriers (4.8%) among hereditary spastic paraplegia unrelated index cases who underwent WES, was significantly higher than among unrelated controls (1.7%; OR=2.88, 95%CI=1.24-6.66, p=0.009). The heterozygous SPG7 p.(Ala510Val) variant was found in 3.7% of index cases vs. 0.85% in unrelated controls (OR=4.42, 95%CI=1.49-13.07, p=0.005). We identified four heterozygous SPG7 variant carriers with an additional pathogenic variant in genes known to cause hereditary spastic paraplegia, compared to zero in controls (OR=19.58, 95%CI=1.05-365.13, p=0.0031; Fisher Exact test with Haldane-Anscombe correction), indicating potential digenic inheritance. We further identified four families with heterozygous variants in SPG7 and SPG7-interacting genes (CACNA1A, AFG3L2 and MORC2). Out of these, there is especially compelling evidence for epistasis between SPG7 and AFG3L2. The p.(Ile705Thr) variant in AFG3L2 is located at the interface between hexamer subunits, in a hotspot of mutations associated with spinocerebellar ataxia type 28 that affect its proteolytic function. Our results provide evidence for complex inheritance in SPG7-associated hereditary spastic paraplegia, which may include recessive and possibly dominant and digenic/epistasis forms of inheritance.

scholarly journals A heterozygous mutation in the CCDC88C gene likely causes early-onset pure hereditary spastic paraplegia: a case report

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ashraf Yahia ◽  
Zhefan Stephen Chen ◽  
Ammar E. Ahmed ◽  
Sara Emad ◽  
Rawaa Adil ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Early Onset ◽  
Late Onset ◽  
In Silico Analysis ◽  
Spinocerebellar Ataxia Type ◽  
Heterozygous Mutation ◽  
Spastic Paraplegia ◽  
Case Presentation ◽  
293 Cells ◽  
Extrapyramidal Signs

Abstract Background CCDC88C is a ubiquitously expressed protein with multiple functions, including roles in cell polarity and the development of dendrites in the nervous system. Bi-allelic mutations in the CCDC88C gene cause autosomal recessive congenital hydrocephalus (OMIM #236600). Studies recently linked heterozygous mutations in CCDC88C to the development of the late-onset spinocerebellar ataxia type 40 (OMIM #616053). Case presentation A 48-year-old Sudanese female presented with pure early onset hereditary spastic paraplegia. Exome sequencing, in-silico analysis, and Sanger sequencing identified the heterozygous NM_001080414.4:c.1993G > A (p.E665K) variant in CCDC88C as a potential cause of her illness. To explore the pathogenicity of the NM_001080414.4:c.1993G > A (p.E665K) variant, we expressed it in human embryonic kidney 293 cells and assessed its effects on apoptosis. In our experiment, NM_001080414.4:c.1993G > A (p.E665K) induced JNK hyper-phosphorylation and enhanced apoptosis. In contrast to previous reports, our patient developed neurological symptoms in early childhood and showed neither features of cerebellar ataxia, extrapyramidal signs, nor evidence of intellectual involvement. Conclusion We, herein, heighlighted the possibility of extending the phenotype associated with variants in CCDC88C to include early-onset pure hereditary spastic paraplegia.

Venous Thromboembolism and High Grade Gliomas

1993 ◽  
Vol 70 (03) ◽  
pp. 393-396 ◽  
Author(s):  
Mandeep S Dhami ◽  
Robert D Bona ◽  
John A Calogero ◽  
Richard M Hellman
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Medical Center ◽  
Significant Risk ◽  
Bleeding Complications ◽  
Fisher Exact Test ◽  
High Grade ◽  
Chi Square ◽  
Exact Test ◽  
High Grade Gliomas

SummaryA retrospective study was done to determine the incidence of and the risk factors predisposing to clinical venous thromboembolism (VTE) in patients treated for high grade gliomas. Medical records of 68 consecutive patients diagnosed and treated at Saint Francis Hospital and Medical Center from January 1986 to June 1991 were reviewed. The follow up was to time of death or at least 6 months (up to December 1991). All clinically suspected episodes of VTE were confirmed by objective tests. Sixteen episodes of VTE were detected in 13 patients for an overall episode rate of 23.5%. Administration of chemotherapy (p = 0.027, two tailed Fisher exact test) and presence of paresis (p = 0.031, two tailed Fisher exact test) were statistically significant risk factors for the development of VTE. Thrombotic events were more likely to occur in the paretic limb and this difference was statistically significant (p = 0.00049, chi square test, with Yates correction). No major bleeding complications were seen in the nine episodes treated with long term anticoagulation.We conclude that venous thromboembolic complications are frequently encountered in patients being treated for high grade gliomas and the presence of paresis and the administration of chemotherapy increases the risk of such complications.

Gait Patterns in Hereditary Spastic Paraplegia

2006 ◽  
Vol 37 (01) ◽  
Author(s):  
L Döderlein ◽  
D Metaxiotis ◽  
S Wolf ◽  
F Braatz
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Spastic Paraplegia ◽  
Gait Patterns

SPG10 in German families with hereditary spastic paraplegia

2006 ◽  
Vol 33 (S 1) ◽  
Author(s):  
R. Schüle ◽  
M. Auer-Grumbach ◽  
J. Kassubek ◽  
S. Klimpe ◽  
T. Klopstock ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Spastic Paraplegia

Electronic cigarettes: How confident and effective are allergists, pulmonologists, and primary care physicians in their practice behavior?

2020 ◽  
Vol 41 (3) ◽  
pp. 192-197
Author(s):  
Sherry S. Zhou ◽  
Alan P. Baptist
Keyword(s):  
Primary Care ◽  
Primary Care Physicians ◽  
Electronic Cigarettes ◽  
The United States ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Knowledge And Beliefs ◽  
Tobacco Cigarette ◽  
Number Of Patients ◽  
Personal Use

Background: There has been a striking increase in electronic cigarette (EC) use in the United States. The beliefs and practices toward ECs among physicians are unknown. Objective: The purpose of this study was to investigate EC practice patterns among allergists, pulmonologists, and primary care physicians. Methods: An anonymous survey was sent to physicians. The survey contained 32 questions and addressed issues related to demographics, cessation counseling behaviors, personal use, and knowledge and beliefs about ECs. Statistical analysis was performed by using analysis of variance, the Pearson χ2 test, Fisher exact test, and logistic regression. Results: A total of 291 physicians completed the survey (222 primary care physicians, 33 pulmonologists, and 36 allergists) for a response rate of 46%. The allergists asked about tobacco cigarette use as frequently as did the pulmonologists and more than the primary care physicians (p < 0.001), but they rarely asked about EC use. The pulmonologists scored highest on self-reported knowledge on ECs, although all the groups answered <40% of the questions correctly. The allergists did not feel as comfortable about providing EC cessation counseling as did the pulmonologists and primary care physicians (p < 0.001). All three groups were equally unlikely to recommend ECs as a cessation tool for tobacco cigarette users. Conclusion: Allergists lacked knowledge and confidence in providing education and cessation counseling for EC users. As the number of patients who use these products continues to increase, there is an urgent need for all physicians to be comfortable and knowledgeable with counseling about ECs.

Perbedaan Kontaminasi Bacteria Staphylococcus sp di Denominasi Uang Kertas Rupiah di Warung Jalan Adi Sucipto Kota Pontianak

2018 ◽  
Vol 1 (2) ◽  
pp. 166
Author(s):  
Sutriswanto Sutriswanto ◽  
Sugito Sugito
Keyword(s):  
Research Method ◽  
Sampling Technique ◽  
Cluster Sampling ◽  
Fisher Exact Test ◽  
Infectious Agents ◽  
Exact Test ◽  
Purposive Sampling ◽  
Paper Money

Abstract: Staphylococcus is a cause of infection. Infection can be transmitted from a source by an indirect through fomite. Paper money can act as transmission of infectious agents, money acts as a fomite. Smaller denominations of value have higher contamination. This study aims to analyze differences in contamination bacterial Staphylococcus sp on denomination of paper money Rp.2.000, 5.000, Rp.10,000 and Rp.20.000 that currently shop on Adi Sucipto street town Pontianak. The research method used in this research is in the form of difference and the sample in this research is denomination of paper money curently with sampling technique using cluster sampling. Checkup of Staphylococcus spon denomination of paper money using rinse method. On these result of study, denomination of paper money Rp.2.000 that is contaminated staphylococcus sp is 80%, denomination of paper money Rp.5.000 that is contaminated staphylococcus sp is 70%, denomination of paper money Rp.10.000 and Rp.20.000 that is contaminated staphylococcus sp is 80%. The data from result of study has been obtained were analyzed statistically by using fisher exact test, the result of p (0,477) >α (0,05) which mean as H1 is rejected. So it can be concluded there is no difference of contamination bacteria staphylococcus sp on denominations of paper money rupiah.Abstrak: Staphylococcus merupakan penyebab terjadinya infeksi. Infeksi dapat ditularkan dari suatu sumber dengan mekanisme tidak langsung melalui fomite. Uang kertas dapat bertindak sebagai transmisi agens infeksius ,uang berperan sebagai fomite. Pecahan uang yang lebih kecil nilainya memiliki kontaminasi yang lebih tinggi. Penelitian ini bertujuan untuk menganalisis perbedaan cemaran bakteri Staphylococcus sp pada pecahan uang kertas Rp.2.000, 5.000, Rp.10.000 dan Rp.20.000 yang beredar di warung jalan Adi Sucipto kota Pontianak. Metode penelitian yang digunakan dalam penelitian berbentuk komperatif dan sampel pada penelitian ini adalah pecahan uang kertas rupiah dengan.teknik pengambilan sampel menggunakan purposive sampling. Pemeriksaan Staphylococcus sp pada pecahan uang kertas rupiah menggunakan metode rinse. Pada hasil penelitian pecahan uang kertas Rp.2.000 yang tercemar staphylococcus sp adalah 80%, pecahan uang kertas Rp.5.000 yang tercemar staphylococcus spadalah 70%, pecahan uang kertas Rp.10.000 dan Rp.20.000 yang tercemar staphylococcus spadalah 50%. Berdasarkan data dari hasil penelitian yang telah didapat dianalisis menggunakan uji statistik fisher exact, didapatkan hasil p (0,477) >α (0,05) yang diartikan sebagai H1 ditolak. Sehingga dapat disimpulkan tidak ada perbedaan cemaran bakteri staphylococcus sp pada pecahan uang kertas rupiah.

Characteristics of Physician Relocation Following Hurricane Katrina

2009 ◽  
Vol 95 (1) ◽  
pp. 6-12
Author(s):  
Kusuma Madamala ◽  
Claudia R. Campbell ◽  
Edbert B. Hsu ◽  
Yu-Hsiang Hsieh ◽  
James James
Keyword(s):  
Hurricane Katrina ◽  
Gulf Coast ◽  
General Medicine ◽  
The United States ◽  
Lessons Learned ◽  
Bivariate Analysis ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Factors Associated ◽  
The Impact

ABSTRACT Introduction: On Aug. 29, 2005, Hurricane Katrina made landfall along the Gulf Coast of the United States, resulting in the evacuation of more than 1.5 million people, including nearly 6000 physicians. This article examines the relocation patterns of physicians following the storm, determines the impact that the disaster had on their lives and practices, and identifies lessons learned. Methods: An Internet-based survey was conducted among licensed physicians reporting addresses within Federal Emergency Management Agency-designated disaster zones in Louisiana and Mississippi. Descriptive data analysis was used to describe respondent characteristics. Multivariate logistic regression was performed to identify the factors associated with physician nonreturn to original practice. For those remaining relocated out of state, bivariate analysis with x2 or Fisher exact test was used to determine factors associated with plans to return to original practice. Results: A total of 312 eligible responses were collected. Among disaster zone respondents, 85.6 percent lived in Louisiana and 14.4 percent resided in Mississippi before the hurricane struck. By spring 2006, 75.6 percent (n = 236) of the respondents had returned to their original homes, whereas 24.4 percent (n = 76) remained displaced. Factors associated with nonreturn to original employment included family or general medicine practice (OR 0.42, 95 percent CI 0.17–1.04; P = .059) and severe or complete damage to the workplace (OR 0.24, 95 percent CI 0.13–0.42; P &lt; .001). Conclusions: A sizeable proportion of physicians remain displaced after Hurricane Katrina, along with a lasting decrease in the number of physicians serving in the areas affected by the disaster. Programs designed to address identified physician needs in the aftermath of the storm may give confidence to displaced physicians to return.

Evolocumab (PCSK9 Inhibitor) in Hereditary Spastic Paraplegia Type 5

2020 ◽  
Author(s):  
Ying Fu ◽  
Xiang Lin ◽  
Yi-Jun Chen ◽  
Lu-Lu Lai ◽  
Yi Lin ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Spastic Paraplegia ◽  
Pcsk9 Inhibitor
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