Genetic Defects in Tight Skin Mice Developing a Scleroderma-Like Syndrome

Heme is central to functions of many biologically important enzymes (hemoproteins). It is an assembly of four porphyrin rings joined through methylene bridges with a central Fe (II). Heme is present in all cells, and its synthesis and degradation balance its amount in the cell. The deregulations of heme networks and incorporation in hemoproteins lead to pathogenic state. This article addresses the detailed structure, biosynthesis, degradation, and transportation associated afflictions to heme. The article is followed by its roles in various diseased conditions where it is produced mainly as the cause of increased hemolysis. It manifests the symptoms in diseases as it is a pro-oxidant, pro-inflammatory and pro-hemolytic agent. We have also discussed the genetic defects that tampered with the biosynthesis, degradation, and transportation of heme. In addition, a brief about the largest hemoprotein group of enzymes- Cytochrome P450 (CYP450) has been discussed with its roles in drug metabolism.

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Biochemical and genetic defects underlying human congenital hypotransferrinemia

The Hematology Journal ◽

10.1038/sj.thj.6200063 ◽

2000 ◽

Vol 1 (6) ◽

pp. 390-398 ◽

Cited By ~ 18

Author(s):

Stefano Goldwurm ◽

Chiara Casati ◽

Natascia Venturi ◽

Simona Strada ◽

Paolo Santambrogio ◽

...

Keyword(s):

Genetic Defects

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Genetic Analysis of a Cohort of 275 Patients with Hyper-IgE Syndromes and/or Chronic Mucocutaneous Candidiasis

Journal of Clinical Immunology ◽

10.1007/s10875-021-01086-4 ◽

2021 ◽

Author(s):

Natalie Frede ◽

Jessica Rojas-Restrepo ◽

Andrés Caballero Garcia de Oteyza ◽

Mary Buchta ◽

Katrin Hübscher ◽

...

Keyword(s):

Screening Method ◽

Cost Effective ◽

Illumina Miseq ◽

Clinical Findings ◽

Genetic Defects ◽

Chronic Mucocutaneous Candidiasis ◽

Mucocutaneous Candidiasis ◽

Serious Infections ◽

History Of ◽

Panel Sequencing

AbstractHyper-IgE syndromes and chronic mucocutaneous candidiasis constitute rare primary immunodeficiency syndromes with an overlapping clinical phenotype. In recent years, a growing number of underlying genetic defects have been identified. To characterize the underlying genetic defects in a large international cohort of 275 patients, of whom 211 had been clinically diagnosed with hyper-IgE syndrome and 64 with chronic mucocutaneous candidiasis, targeted panel sequencing was performed, relying on Agilent HaloPlex and Illumina MiSeq technologies. The targeted panel sequencing approach allowed us to identify 87 (32 novel and 55 previously described) mutations in 78 patients, which generated a diagnostic success rate of 28.4%. Specifically, mutations in DOCK8 (26 patients), STAT3 (21), STAT1 (15), CARD9 (6), AIRE (3), IL17RA (2), SPINK5 (3), ZNF341 (2), CARMIL2/RLTPR (1), IL12RB1 (1), and WAS (1) have been detected. The most common clinical findings in this cohort were elevated IgE (81.5%), eczema (71.7%), and eosinophilia (62.9%). Regarding infections, 54.7% of patients had a history of radiologically proven pneumonia, and 28.3% have had other serious infections. History of fungal infection was noted in 53% of cases and skin abscesses in 52.9%. Skeletal or dental abnormalities were observed in 46.2% of patients with a characteristic face being the most commonly reported feature (23.1%), followed by retained primary teeth in 18.9% of patients. Targeted panel sequencing provides a cost-effective first-line genetic screening method which allows for the identification of mutations also in patients with atypical clinical presentations and should be routinely implemented in referral centers.

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The Molecular Bases Study of the Inherited Diseases for the Health Maintenance of the Beef Cattle

Genes ◽

10.3390/genes12050678 ◽

2021 ◽

Vol 12 (5) ◽

pp. 678

Author(s):

Elena Konovalova ◽

Olga Romanenkova ◽

Olga Kostyunina ◽

Elena Gladyr

Keyword(s):

Dna Analysis ◽

Genetic Defects ◽

Health Maintenance ◽

Angus Cattle ◽

Hereford Cattle ◽

Pcr Rflp ◽

Cattle Herds ◽

Molecular Bases ◽

Further Development

The article highlighted the problem of meat cattle genetic defects. The aim was the development of DNA tests for some genetic defects diagnostics, the determination of the animal carriers and their frequencies tracking in time. The 1490 DNA samples from the Aberdeen Angus (n = 701), Hereford (n = 385), Simmental (n = 286) and Belgian Blue (n = 118) cattle have been genotyped on the genetic defects by newly created and earlier developed DNA tests based on AS-PCR and PCR-RFLP methods. The Aberdeen Angus cattle genotyping has revealed 2.38 ± 0.31% AMC-cows and 1.67 ± 0.19 % AMC-bulls, 0.65 ± 0.07% DDC-cows and 0.90 ± 0.10% DDC-bulls. The single animals among the Hereford cattle were carriers of MSUD and CWH (on 0.27 ± 0.05%), ICM and HY (on 0.16 ± 0.03%). The Simmental cattle were free from OS. All Belgian Blue livestock were M1- and 0.84%-CMD1-carriers. The different ages Aberdeen Angus cattle genotyping has shown the tendency of the AMC- and DDC frequencies to increase in the later generations. The statistically significant increase of DDC of 1.17% in the cows’ population born in 2019 compared to those born in 2015 allows concluding the further development of the DNA analysis-based measures preventing the manifestation of the genetic anomalies in meat cattle herds is necessary.

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DNA methylation epi-signature is associated with two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome

Clinical Epigenetics ◽

10.1186/s13148-020-00990-7 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

L. C. Schenkel ◽

E. Aref-Eshghi ◽

K. Rooney ◽

J. Kerkhof ◽

M. A. Levy ◽

...

Keyword(s):

Dna Methylation ◽

Critical Region ◽

Deletion Syndrome ◽

Genetic Defects ◽

Chromosome 22 ◽

Incomplete Penetrance ◽

Variable Size ◽

Variable Expressivity ◽

Genome Wide ◽

22Q13.3 Deletion Syndrome

Abstract Background Phelan-McDermid syndrome is characterized by a range of neurodevelopmental phenotypes with incomplete penetrance and variable expressivity. It is caused by a variable size and breakpoint microdeletions in the distal long arm of chromosome 22, referred to as 22q13.3 deletion syndrome, including the SHANK3 gene. Genetic defects in a growing number of neurodevelopmental genes have been shown to cause genome-wide disruptions in epigenomic profiles referred to as epi-signatures in affected individuals. Results In this study we assessed genome-wide DNA methylation profiles in a cohort of 22 individuals with Phelan-McDermid syndrome, including 11 individuals with large (2 to 5.8 Mb) 22q13.3 deletions, 10 with small deletions (< 1 Mb) or intragenic variants in SHANK3 and one mosaic case. We describe a novel genome-wide DNA methylation epi-signature in a subset of individuals with Phelan-McDermid syndrome. Conclusion We identified the critical region including the BRD1 gene as responsible for the Phelan-McDermid syndrome epi-signature. Metabolomic profiles of individuals with the DNA methylation epi-signature showed significantly different metabolomic profiles indicating evidence of two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome.

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