Unusual phenotypic variability within the same family: Variable penetrance and variable clinical expression

1996 ◽  
Vol 6 ◽  
pp. S39 ◽  
Author(s):  
José Barros ◽  
Teresa Coelho ◽  
Luísa Lobato ◽  
Alda Sousa
Keyword(s):  
Phenotypic Variability ◽  
Clinical Expression ◽  
Family Variable ◽  
Variable Penetrance

scholarly journals The Region Centromeric to HLA-C Is a Key Region for Understanding the Phenotypic Variability of Psoriatic Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Rubén Queiro ◽  
Patricia Tejón ◽  
Sara Alonso ◽  
Pablo Coto ◽  
Carlos López-Larrea ◽  
...  
Keyword(s):  
Disease Risk ◽  
Phenotypic Variability ◽  
Interphalangeal Joint ◽  
Healthy Controls ◽  
Polymorphic Markers ◽  
Distal Interphalangeal Joint ◽  
Clinical Expression ◽  
Risk Genes ◽  
Distal Interphalangeal

With the aim of clarifying the role of several polymorphisms around the HLA-C locus in the clinical expression of PsA, the distribution of several polymorphic markers and genes located around the HLA-C locus was analyzed in a well-established cohort of 110 patients with PsA, 50 patients with psoriasis alone, and 110 healthy controls. The frequency of these genes was also analyzed by PsA articular models, based on three main subgroups: oligoarthritis, polyarthritis, and spondylitis. Distal interphalangeal joint (DIP) involvement was associated with the presence of MICB-CA20 (OR 6.0, 95% CI: 1.58–22.69, P=0.005). HLA-DRB*07 was associated with oligoarticular forms of PsA (OR 4.1, 95% CI: 1.8–9.3, P=0.0007). The spondylitic forms overexpressed the antigen HLA-B*27 (OR 5.7, 95% CI: 2.4–13.6, P=0.0001). MICA-A5.1 showed association with polyarthritis (OR 3.7, 95% CI: 1.5–8.8, P=0.006). Genes telomeric to HLA-C were overexpressed in psoriasis but not in PsA subphenotypes. This study shows that the region centromeric to HLA-C is a key region that expresses not only disease risk genes but also genes that help explain the phenotypic variability of PsA.

scholarly journals Epigenomic analysis of KLF1 haploinsufficiency in primary human erythroblasts

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Steven Heshusius ◽  
Laura Grech ◽  
Nynke Gillemans ◽  
Rutger W. W. Brouwer ◽  
Xander T. den Dekker ◽  
...  
Keyword(s):  
Gene Expression Analysis ◽  
Therapeutic Strategy ◽  
Phenotypic Variability ◽  
Fetal Hemoglobin ◽  
Transcriptional Regulators ◽  
Chromatin Accessibility ◽  
Erythroid Progenitors ◽  
Wide Range ◽  
Hereditary Persistence ◽  
Variable Penetrance

AbstractHaploinsufficiency for the erythroid-specific transcription factor KLF1 is associated with hereditary persistence of fetal hemoglobin (HPFH). Increased HbF ameliorates the symptoms of β-hemoglobinopathies and downregulation of KLF1 activity has been proposed as a potential therapeutic strategy. However, the feasibility of this approach has been challenged by the observation that KLF1 haploinsufficient individuals with the same KLF1 variant, within the same family, display a wide range of HbF levels. This phenotypic variability is not readily explained by co-inheritance of known HbF-modulating variants in the HBB, HBS1L-MYB and/or BCL11A loci. We studied cultured erythroid progenitors obtained from Maltese individuals in which KLF1 p.K288X carriers display HbF levels ranging between 1.3 and 12.3% of total Hb. Using a combination of gene expression analysis, chromatin accessibility assays and promoter activity tests we find that variation in expression of the wildtype KLF1 allele may explain a significant part of the variability in HbF levels observed in KLF1 haploinsufficiency. Our results have general bearing on the variable penetrance of haploinsufficiency phenotypes and on conflicting interpretations of pathogenicity of variants in other transcriptional regulators such as EP300, GATA2 and RUNX1.

Large phenotypic variability of diabetes due to ABCC8 gene mutation illustrated by the paradigm of a family

2019 ◽  
Author(s):  
Theocharis Koufakis ◽  
Amalia Sertedaki ◽  
Elizabeth-Barbara Tatsi ◽  
Christina-Maria Trakatelli ◽  
Spyridon Karras ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Phenotypic Variability ◽  
Abcc8 Gene

Twenty-five years of familial glucocorticoid deficiency: genotypic and phenotypic variability

2019 ◽  
Author(s):  
CJ Smith ◽  
AV Maharaj ◽  
R Prasad ◽  
C Hughes ◽  
Y Qamar ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Glucocorticoid Deficiency

Formation and composition of training flax collection

2020 ◽  
pp. 61-71
Author(s):  
L.M. Kryvosheieva ◽  
V.I. Chuchvaha ◽  
N.M. Kandyba
Keyword(s):  
Plant Breeding ◽  
Gene Pool ◽  
Phenotypic Variability ◽  
Plant Genetic Resources ◽  
Field Measurements ◽  
Educational Process ◽  
Educational Institutions ◽  
Economic Traits ◽  
Wide Range ◽  
History Of

Aim. Based on the results of multi-year research into the flax gene pool, to form a flax training collection to provide breeding scientific organizations and educational institutions with collection samples as well as with information about the bast crop gene pool. Results and Discussion. The studies were conducted in the crop rotation fields for breeding and seed production of the Institute of Bast Crops of the NAAS (Hlukhiv, Sumska Oblast) in 1992-2018. The field measurements and laboratory analyses were carried out in accordance with conventional methods of field and laboratory studies of collection flax samples.The article presents the results on the formation of a training collection of flax at the Institute of Bast Crops of the NAAS, which has 117 accessions (11 botanical species and three varieties) from 22 countries. In addition to species diversity, the collection includes accessions with different levels of expression of valuable economic and biological characteristics. It also includes accessions selected by phenotypic variability of individual characters or their combinations. The multi-year research into the flax collection accessions resulted in identification of sources of highly-expressed valuable economic traits, which are of interest for the plant breeding course. The history of flax breeding in Ukraine is shown, where breeding varieties that are most widespread or were significant breeding achievements in solving certain problems, are presented. The collection can be used as a visual aid for the plant breeding course in educational programs; in addition, it can provide starting material for scientific and educational institutions. The collection is registered with the National Center for Plant Genetic Resources of Ukraine (certificate No. 00273 dated 04/11/2019). Conclusions. The studies of accessions from the national flax collection allowed us to build up a training collection and register it with the NCPGRU. The collection represents a wide range of biological and economic features of the gene pool of this crop. The collection can be used in the educational process of educational agricultural and biological institutions. The multi-year research into the national flax collection resulted in identification of sources of highly-expressed valuable economic traits, which are of interest to the plant breeding course. The history of flax breeding in Ukraine got covered, and breeding varieties that are most widespread or were significant breeding achievements in solving certain problems are presented.

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