scholarly journals Skin exhibits of Dark Ronald XX are homozygous wild type at the Warmblood fragile foal syndrome causative missense variant position in lysyl hydroxylase gene PLOD1

2020 ◽  
Vol 51 (5) ◽  
pp. 838-840 ◽  
Author(s):  
Xuying Zhang ◽  
Marc Hirschfeld ◽  
Renate Schafberg ◽  
Hermann Swalve ◽  
Bertram Brenig
Keyword(s):  
Missense Variant ◽  
Wild Type ◽  
Lysyl Hydroxylase ◽  
Hydroxylase Gene

scholarly journals Heterozygous missense RAD21 variant in a peripheral sclerocornea pedigree

2019 ◽  
Author(s):  
Bi Ning Zhang ◽  
Tommy Chung Yan Chan ◽  
Pancy Oi Sin Tam ◽  
Yu Liu ◽  
Chi Pui Pang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Genetic Variant ◽  
Mrna Level ◽  
Missense Variant ◽  
Genetic Alterations ◽  
Chinese Family ◽  
Wild Type ◽  
Whole Exome ◽  
Rare Congenital Disorder ◽  
Corneal Diameter

AbstractBackgroundSclerocomea is a rare congenital disorder characterized with cornea opacification. We identified a heterozygous missense RAD21 variant in a non-cons anguineous Chinese family with multiple peripheral sclerocomea patients spanning across three generations inherited in an autosomal dominant manner.MethodsComprehensive ophthalmic examinations were conducted on all 14 members. Whole exome sequencing was used to identify the genetic alterations in the affected pedigree members. Lymphoblastoid cell lines (LCLs) were established using blood samples from all members. Cleavage of RAD21 protein was quantified in these cell lines.ResultsAll affected individuals showed features of scleralization over the peripheral cornea of both eyes. Mean horizontal and vertical corneal diameter were significantly decreased in the affected members. Significant differences were also observed on mean apex pachymetry between affected and unaffected subjects. A RAD21C1348T variant was co-segregated with affected members. Both the wild-type allele and the missense variant were expressed at the mRNA level. This variant caused RAD21 R450C substitution at the separase cleavage site, which led to reduced RAD21 cleavage.ConclusionWe believe this is the first report of genetic variant in sclerocornea without other syndromes. Further work is needed to confirm the RAD21R450C variant with sclerocomea.

scholarly journals A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene.

1994 ◽  
Vol 93 (4) ◽  
pp. 1716-1721 ◽  
Author(s):  
V T Ha ◽  
M K Marshall ◽  
L J Elsas ◽  
S R Pinnell ◽  
H N Yeowell
Keyword(s):  
Compound Heterozygote ◽  
Syndrome Type ◽  
Ehlers Danlos Syndrome ◽  
Lysyl Hydroxylase ◽  
Hydroxylase Gene ◽  
Danlos Syndrome

Characterization of the regulatory and minoxidil-responsive elements in the 5′ flanking region of the lysyl hydroxylase gene

1998 ◽  
Vol 16 ◽  
pp. S134
Author(s):  
S.F. Thai ◽  
S.R. Pinnell ◽  
H.N. Yeowell
Keyword(s):  
Lysyl Hydroxylase ◽  
Hydroxylase Gene ◽  
Flanking Region

scholarly journals EAP1 regulation of GnRH promoter activity is important for human pubertal timing

2019 ◽  
Vol 28 (8) ◽  
pp. 1357-1368 ◽  
Author(s):  
Alessandra Mancini ◽  
Sasha R Howard ◽  
Claudia P Cabrera ◽  
Michael R Barnes ◽  
Alessia David ◽  
...  
Keyword(s):  
Chromatin Immunoprecipitation ◽  
Pubertal Timing ◽  
Missense Variant ◽  
Luciferase Reporter ◽  
Delayed Puberty ◽  
Wild Type ◽  
Protein Levels ◽  
Pathogenic Variants ◽  
Expression Studies ◽  
Whole Exome

Abstract The initiation of puberty is orchestrated by an augmentation of gonadotropin-releasing hormone (GnRH) secretion from a few thousand hypothalamic neurons. Recent findings have indicated that the neuroendocrine control of puberty may be regulated by a hierarchically organized network of transcriptional factors acting upstream of GnRH. These include enhanced at puberty 1 (EAP1), which contributes to the initiation of female puberty through transactivation of the GnRH promoter. However, no EAP1 mutations have been found in humans with disorders of pubertal timing. We performed whole-exome sequencing in 67 probands and 93 relatives from a large cohort of familial self-limited delayed puberty (DP). Variants were analyzed for rare, potentially pathogenic variants enriched in case versus controls and relevant to the biological control of puberty. We identified one in-frame deletion (Ala221del) and one rare missense variant (Asn770His) in EAP1 in two unrelated families; these variants were highly conserved and potentially pathogenic. Expression studies revealed Eap1 mRNA abundance in peri-pubertal mouse hypothalamus. EAP1 binding to the GnRH1 promoter increased in monkey hypothalamus at the onset of puberty as determined by chromatin immunoprecipitation. Using a luciferase reporter assay, EAP1 mutants showed a reduced ability to trans-activate the GnRH promoter compared to wild-type EAP1, due to reduced protein levels caused by the Ala221del mutation and subcellular mislocation caused by the Asn770His mutation, as revealed by western blot and immunofluorescence, respectively. In conclusion, we have identified the first EAP1 mutations leading to reduced GnRH transcriptional activity resulting in a phenotype of self-limited DP.

scholarly journals Functional investigation of the coronary artery disease gene SVEP1

2020 ◽  
Vol 115 (6) ◽  
Author(s):  
Michael J. Winkler ◽  
Philipp Müller ◽  
Amin M. Sharifi ◽  
Jana Wobst ◽  
Hanna Winter ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Vascular Inflammation ◽  
Missense Variant ◽  
Leukocyte Recruitment ◽  
Wild Type ◽  
Cellular Source ◽  
Elevated Expression ◽  
Artery Disease

AbstractA missense variant of the sushi, von Willebrand factor type A, EGF and pentraxin domain containing protein 1 (SVEP1) is genome-wide significantly associated with coronary artery disease. The mechanisms how SVEP1 impacts atherosclerosis are not known. We found endothelial cells (EC) and vascular smooth muscle cells to represent the major cellular source of SVEP1 in plaques. Plaques were larger in atherosclerosis-prone Svep1 haploinsufficient (ApoE−/−Svep1+/−) compared to Svep1 wild-type mice (ApoE−/−Svep1+/+) and ApoE−/−Svep1+/− mice displayed elevated plaque neutrophil, Ly6Chigh monocyte, and macrophage numbers. We assessed how leukocytes accumulated more inside plaques in ApoE−/−Svep1+/− mice and found enhanced leukocyte recruitment from blood into plaques. In vitro, we examined how SVEP1 deficiency promotes leukocyte recruitment and found elevated expression of the leukocyte attractant chemokine (C-X-C motif) ligand 1 (CXCL1) in EC after incubation with missense compared to wild-type SVEP1. Increasing wild-type SVEP1 levels silenced endothelial CXCL1 release. In line, plasma Cxcl1 levels were elevated in ApoE−/−Svep1+/− mice. Our studies reveal an atheroprotective role of SVEP1. Deficiency of wild-type Svep1 increased endothelial CXCL1 expression leading to enhanced recruitment of proinflammatory leukocytes from blood to plaque. Consequently, elevated vascular inflammation resulted in enhanced plaque progression in Svep1 deficiency.

scholarly journals Analysis of Missense Variants in the Human Histamine Receptor Family Reveals Increased Constitutive Activity of E4106.30×30K Variant in the Histamine H1 Receptor

2021 ◽  
Vol 22 (7) ◽  
pp. 3702
Author(s):  
Xiaoyuan Ma ◽  
Marta Arimont Segura ◽  
Barbara Zarzycka ◽  
Henry F. Vischer ◽  
Rob Leurs
Keyword(s):  
G Protein ◽  
Missense Variant ◽  
Histamine Receptor ◽  
Structural Basis ◽  
Constitutive Activity ◽  
Wild Type ◽  
H1 Receptor ◽  
Histamine H1 Receptor ◽  
Missense Variants ◽  
Receptor Family

The Exome Aggregation Consortium has collected the protein-encoding DNA sequences of almost 61,000 unrelated humans. Analysis of this dataset for G protein-coupled receptor (GPCR) proteins (available at GPCRdb) revealed a total of 463 naturally occurring genetic missense variations in the histamine receptor family. In this research, we have analyzed the distribution of these missense variations in the four histamine receptor subtypes concerning structural segments and sites important for GPCR function. Four missense variants R1273.52×52H, R13934.57×57H, R4096.29×29H, and E4106.30×30 K, were selected for the histamine H1 receptor (H1R) that were hypothesized to affect receptor activity by interfering with the interaction pattern of the highly conserved D(E)RY motif, the so-called ionic lock. The E4106.30×30 K missense variant displays higher constitutive activity in G protein signaling as compared to wild-type H1R, whereas the opposite was observed for R1273.52×52H, R13934.57×57H, and R4096.29×29H. The E4106.30×30 K missense variant displays a higher affinity for the endogenous agonist histamine than wild-type H1R, whereas antagonist affinity was not affected. These data support the hypothesis that the E4106.30×30 K mutation shifts the equilibrium towards active conformations. The study of these selected missense variants gives additional insight into the structural basis of H1R activation and, moreover, highlights that missense variants can result in pharmacologically different behavior as compared to wild-type receptors and should consequently be considered in the drug discovery process.

A compound heterozygote patient with Ehlers-Danlos syndrome type VI has a deletion in one allele and a splicing defect in the other allele of the lysyl hydroxylase gene

1998 ◽  
Vol 11 (1) ◽  
pp. 55-61 ◽  
Author(s):  
Birgitta Pousi ◽  
Timo Hautala ◽  
James C. Hyland ◽  
Jukka Schröter ◽  
Beate Eckes ◽  
...  
Keyword(s):  
Compound Heterozygote ◽  
The Other ◽  
Syndrome Type ◽  
Ehlers Danlos Syndrome ◽  
Lysyl Hydroxylase ◽  
Hydroxylase Gene ◽  
Splicing Defect ◽  
Danlos Syndrome

Alu-alu recombination results in duplication of seven exons in the lysyl hydroxylase gene from a patient with the type VI variant of Ehlers-Danlos syndrome

1994 ◽  
Vol 14 (5) ◽  
pp. 399 ◽  
Author(s):  
B. Pousi ◽  
T. Hautala ◽  
J. Heikkinen ◽  
L. Pajunen ◽  
K.I. Kivirikko ◽  
...  
Keyword(s):  
Ehlers Danlos Syndrome ◽  
Lysyl Hydroxylase ◽  
Hydroxylase Gene ◽  
Danlos Syndrome

A patient with ehlers danlos syndrome type VI is a compound heterozygote for the lysyl hydroxylase gene

1993 ◽  
Vol 6 (1) ◽  
pp. 4
Author(s):  
Heather N. Yeowell ◽  
Van Ha ◽  
Sheldon R. Pinnell
Keyword(s):  
Compound Heterozygote ◽  
Syndrome Type ◽  
Ehlers Danlos Syndrome ◽  
Lysyl Hydroxylase ◽  
Hydroxylase Gene ◽  
Danlos Syndrome
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