The molecular genetics of UV-Sensitive syndrome; a rare dermal anomaly

UV-Sensitive syndrome (UVSS) is a rare skin disorder that is characterized by heterogeneous phenotypic spectrum of skin freckling, telangiectasia and acute sunburn. UV-Sensitive syndrome (UVSS) usually inherit in autosomal recessive pattern. So far, only 18 patients from nine different families (i.e. Japanese, French, Israeli, Iranian and Pakistani) have been reported in the scientific literature. Its precise prevalence is still unknown, but according to an estimation, it prevails with the ratio of 1:100,000 worldwide. Until now, only three genes have been reported to be involved in UV-Sensitive syndrome, including ERCC6, ERCC8 and UVSSA. Among these genes, UVSSA is reported to be more prevalent among different ethnicities, including Pakistan as well. Physiologically, UV-Sensitive syndrome genes are involved in transcription-coupled nucleotide excision pathway. In order to reduce the disease severity, Continuous..

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Updated overview on the interplay between obesity and COVID-19

Diagnosis ◽

10.1515/dx-2020-0111 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Diletta Onorato ◽

Giovanni Carpenè ◽

Giuseppe Lippi ◽

Mairi Pucci

Keyword(s):

Disease Severity ◽

Clinical Characteristics ◽

Literature Search ◽

Scientific Literature ◽

Population Sample ◽

Obese Patients ◽

Health Crisis ◽

Keywords Obesity ◽

Negative Prognostic Factor ◽

The Impact

AbstractThe worldwide spread of coronavirus disease 2019 (COVID-19) has generated a global health crisis and more than a million deaths so far. Epidemiological and clinical characteristics of COVID-19 are increasingly reported, along with its potential relationship with overweight and/or obesity. Therefore, we aim here to review the current scientific literature on the impact of overweight and/or obesity among hospitalized patients who have developed severe or critical forms of COVID-19. Following PRISMA guidelines, our literature search identified over 300 scientific articles using the keywords “obesity” and “COVID-19”, 22 of which were finally selected for reporting useful information on the association between overweight/obesity and disease severity. In particular, in 11 out of the 14 studies (79%) which evaluated the association between obesity and disease severity providing also a risk estimate (i.e., the odd ratio; OR), the OR value was constantly >2. Although the studies were found to be heterogeneous in terms of design, population, sample size and endpoints, in most cases a significant association was found between obesity and the risk of progressing to severe COVID-19 illness, intensive care unit admission and/or death. We can hence conclude that an increased body mass index shall be considered a negative prognostic factor in patients with COVID-19, and more aggressive prevention or treatment shall hence be reserved to overweight and/or obese patients.

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ANK3 related neurodevelopmental disorders: expanding the spectrum of heterozygous loss-of-function variants

Neurogenetics ◽

10.1007/s10048-021-00655-4 ◽

2021 ◽

Author(s):

Katja Kloth ◽

Bernarda Lozic ◽

Julia Tagoe ◽

Mariëtte J. V. Hoffer ◽

Amelie Van der Ven ◽

...

Keyword(s):

Autosomal Recessive ◽

Neuronal Development ◽

Autosomal Dominant ◽

Tissue Expression ◽

Autism Spectrum ◽

Loss Of Function ◽

Ankyrin G ◽

Phenotypic Spectrum ◽

And Function ◽

Neurodevelopmental Phenotype

AbstractANK3 encodes multiple isoforms of ankyrin-G, resulting in variegated tissue expression and function, especially regarding its role in neuronal development. Based on the zygosity, location, and type, ANK3 variants result in different neurodevelopmental phenotypes. Autism spectrum disorder has been associated with heterozygous missense variants in ANK3, whereas a more severe neurodevelopmental phenotype is caused by isoform-dependent, autosomal-dominant, or autosomal-recessive loss-of-function variants. Here, we present four individuals affected by a variable neurodevelopmental phenotype harboring a heterozygous frameshift or nonsense variant affecting all ANK3 transcripts. Thus, we provide further evidence of an isoform-based phenotypic continuum underlying ANK3-associated pathologies and expand its phenotypic spectrum.

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Molecular Pathophysiology of Autosomal Recessive Polycystic Kidney Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22126523 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6523

Author(s):

Adrian Cordido ◽

Marta Vizoso-Gonzalez ◽

Miguel A. Garcia-Gonzalez

Keyword(s):

Kidney Disease ◽

Polycystic Kidney Disease ◽

Molecular Basis ◽

Autosomal Recessive ◽

Polycystic Kidney ◽

Phenotypic Spectrum ◽

New Gene ◽

Stage Renal Disease ◽

End Stage ◽

Molecular Pathophysiology

Autosomal recessive polycystic kidney disease (ARPKD) is a rare disorder and one of the most severe forms of polycystic kidney disease, leading to end-stage renal disease (ESRD) in childhood. PKHD1 is the gene that is responsible for the vast majority of ARPKD. However, some cases have been related to a new gene that was recently identified (DZIP1L gene), as well as several ciliary genes that can mimic a ARPKD-like phenotypic spectrum. In addition, a number of molecular pathways involved in the ARPKD pathogenesis and progression were elucidated using cellular and animal models. However, the function of the ARPKD proteins and the molecular mechanism of the disease currently remain incompletely understood. Here, we review the clinics, treatment, genetics, and molecular basis of ARPKD, highlighting the most recent findings in the field.

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Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis

Blood ◽

10.1182/blood.v100.2.692 ◽

2002 ◽

Vol 100 (2) ◽

pp. 692-694 ◽

Cited By ~ 113

Author(s):

Daniel F. Wallace ◽

Palle Pedersen ◽

Jeannette L. Dixon ◽

Peter Stephenson ◽

Jeffrey W. Searle ◽

...

Keyword(s):

Iron Transport ◽

Autosomal Recessive ◽

Iron Homeostasis ◽

Autosomal Dominant ◽

Novel Mutation ◽

Hfe Gene ◽

Excess Iron ◽

Chromosome 1Q ◽

Australian Family ◽

Autosomal Recessive Pattern

Abstract Hemochromatosis is a common disorder characterized by excess iron absorption and accumulation of iron in tissues. Usually hemochromatosis is inherited in an autosomal recessive pattern and is caused by mutations in the HFE gene. Less common non-HFE–related forms of hemochromatosis have been reported and are caused by mutations in the transferrin receptor 2 gene and in a gene localized to chromosome 1q. Autosomal dominant forms of hemochromatosis have also been described. Recently, 2 mutations in theferroportin1 gene, which encodes the iron transport protein ferroportin1, have been implicated in families with autosomal dominant hemochromatosis from the Netherlands and Italy. We report the finding of a novel mutation (V162del) in ferroportin1 in an Australian family with autosomal dominant hemochromatosis. We propose that this mutation disrupts the function of the ferroportin1 protein, leading to impaired iron homeostasis and iron overload.

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The Molecular Genetics of Autosomal Recessive Nonsyndromic Intellectual Disability: a Mutational Continuum and Future Recommendations

Annals of Human Genetics ◽

10.1111/ahg.12176 ◽

2016 ◽

Vol 80 (6) ◽

pp. 342-368 ◽

Cited By ~ 8

Author(s):

Muzammil Ahmad Khan ◽

Saadullah Khan ◽

Christian Windpassinger ◽

Muhammad Badar ◽

Zafar Nawaz ◽

...

Keyword(s):

Intellectual Disability ◽

Molecular Genetics ◽

Autosomal Recessive

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Pierquin Syndrome: Report of a New Case

Journal of Pediatric Neurology ◽

10.1055/s-0040-1710397 ◽

2020 ◽

Author(s):

Francisco Cammarata-Scalisi ◽

Colin Eric Willoughby ◽

María Angelina Lacruz- Rengel ◽

Enrico Silvio Bertini ◽

Michele Callea

Keyword(s):

Congenital Heart ◽

Autosomal Recessive ◽

Malformation Syndrome ◽

Postaxial Polydactyly ◽

Phenotypic Spectrum ◽

Dandy Walker Malformation ◽

Rare Malformation ◽

Walker Malformation ◽

Genetic Entity ◽

Syndrome Report

AbstractPierquin syndrome is a rare genetic entity characterized by the association of Dandy–Walker malformation and postaxial polydactyly. The incidence is uncertain with only six cases previously reported in the literature. In this study, we reported a new case of Pierquin syndrome born from consanguineous parents, characterized by Dandy–Walker malformation, postaxial polydactyly, and congenital heart disease. The case reinforces an autosomal recessive modality of inheritance and expands the phenotypic spectrum of this rare malformation syndrome.

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Warmblood fragile foal syndrome causative single nucleotide polymorphism frequency in horses in Ireland

Irish Veterinary Journal ◽

10.1186/s13620-021-00206-1 ◽

2021 ◽

Vol 74 (1) ◽

Author(s):

Áine Rowe ◽

Sharon Flanagan ◽

Gerald Barry ◽

Lisa M. Katz ◽

Elizabeth A. Lane ◽

...

Keyword(s):

Autosomal Recessive ◽

Scientific Literature ◽

Genetic Test ◽

Low Frequency ◽

Autosomal Recessive Disorder ◽

Causative Mutation ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Hair Samples ◽

Heterozygous Carriers

Abstract Background Warmblood Fragile Foal Syndrome (WFFS) is an autosomal recessive disorder caused by a mutation in the procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) gene. Homozygosity for the mutation results in defective collagen synthesis which clinically manifests as the birth of non viable or still born foals with abnormally fragile skin. While the mutation has been identified in non Warmblood breeds including the Thoroughbred, to date all homozygous clinically affected cases reported in the scientific literature are Warmblood foals. The objective of this study was to investigate the carrier frequency of the mutation in the Thoroughbred and sport horse populations in Ireland. Methods A test was developed at the UCD School of Veterinary Medicine using real-time PCR to amplify the PLOD1 gene c.2032G > A variant. A subset of the samples was also submitted to an external laboratory with a licensed commercial WFFS genetic test. Results Warmblood Fragile Foal Syndrome genotyping was performed on hair samples from 469 horses representing 6 different breeds. Six of 303 (1.98%) sport horses tested and three of 109 (2.75%) Thoroughbreds tested were heterozygous for the WFFS polymorphism (N/WFFS). The WFFS polymorphism was not identified in the Standardbred, Cob, Connemara, or other pony breeds. Conclusions The study identified a low frequency of the WFFS causative mutation in sport horses and Thoroughbreds in Ireland, highlighting the importance of WFFS genetic testing in order to identify phenotypically normal heterozygous carriers and to prevent the birth of nonviable foals.

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Detection, not mortality, constrains the evolution of virulence

10.1101/2021.11.14.468516 ◽

2021 ◽

Author(s):

David A Kennedy

Keyword(s):

Mathematical Model ◽

Disease Severity ◽

Behavioral Change ◽

Scientific Literature ◽

Empirical Support ◽

Infectious Period ◽

Trade Off ◽

Evolution Of Virulence ◽

Host Mortality

Why would a pathogen evolve to kill its hosts when killing a host ends a pathogen's own opportunity for transmission? A vast body of scientific literature has attempted to answer this question using "trade-off theory," which posits that host mortality persists due to its cost being balanced by benefits of other traits that correlate with host mortality. The most commonly invoked trade-off is the mortality-transmission trade-off, where increasingly harmful pathogens are assumed to transmit at higher rates from hosts while the hosts are alive, but the pathogens truncate their infectious period by killing their hosts. Here I show that costs of mortality are too small to plausibly constrain the evolution of disease severity except in systems where survival is rare. I alternatively propose that disease severity can be much more readily constrained by a cost of behavioral change due to the detection of infection, whereby increasingly harmful pathogens have increasing likelihood of detection and behavioral change following detection, thereby limiting opportunities for transmission. Using a mathematical model, I show the conditions under which detection can limit disease severity. Ultimately, this argument may explain why empirical support for trade-off theory has been limited and mixed.

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AN AYURVEDIC MANAGEMENT OF SPINAL MUSCULAR ATROPHY (SMA) – A CASE STUDY

November 2020 - International Ayurvedic Medical Journal ◽

10.46607/iamj4309112021 ◽

2021 ◽

Vol 9 (11) ◽

pp. 2897-2902

Author(s):

Raheena B ◽

Shaila Borannavar ◽

Ananta S Desai

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Neurons ◽

Autosomal Recessive ◽

Muscular Atrophy ◽

Genetic Disorder ◽

The Body ◽

Erect Posture ◽

Smn1 Gene ◽

Autosomal Recessive Pattern

Spinal Muscular Atrophy (SMA) is the second leading genetic disorder inherited in the autosomal recessive pattern due to the absence of the SMN1 gene characterized by loss of motor neurons and progressive muscle wasting, often leading to dependent life and decreased life span. In Ayurveda, this condition can be considered as Kulaja Vyadhi wherein the patient’s Mamsa and Snayu is affected by Vata. This can be regarded as Mamsa-Snayugata Sarvanga Vata. It is said that Prakruta Vata dosha is the life, it is the strength, it is the sustainer of the body, it holds the body and life together. If it is Vikruta it produces Sankocha, Khanja, Kubjatva, Pangutva, Khalli and Soshana of Anga. So, in this disease aggravated Vata does the vitiation of Mamsa and Snayu thus leading to Soshana of both, resulting in Stambha, Nischalikarana of Avayava. A 21years female patient was admitted to our I.P.D with c/o of reduced strength in all four limbs leading to the inability to walk and to maintain erect posture during standing and sitting positions. Based on Ayurvedic principles the patient was initially subjected to Avaranahara Chikitsa followed by Brimhana line of management. Keywords: Mamsagata vata, Snayugata vata, Sarvanga vata, Spinal muscular atrophy (SMA)

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