|
Acute intermittent porphyria
|
1.000 |
Biomarker
|
disease |
BEFREE |
Our findings demonstrate the great potential of these hits for the development of a pharmacological chaperone-based corrective treatment of AIP by enhancing wild-type HMBS function independently of the patients' specific mutation.
|
31810863 |
2020 |
|
Acute intermittent porphyria
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
To investigate the dramatically different manifestations, knock-in mice with human HD-AIP missense mutations c.500G>A (p.Arg167Glu) or c.518_519GC>AG (p.Arg173Glu), designated R167Q or R173Q mice, respectively, were generated and compared with the previously established T1/T2 mice with ~30% residual HMBS activity and the heterozygous AIP phenotype.
|
30615115 |
2019 |
|
Acute intermittent porphyria
|
1.000 |
Biomarker
|
disease |
BEFREE |
In a recent study published in Nature Medicine (Published online October 8, 2018. doi.org/10.1038/s41591-018-0199-z), the intravenous delivery of human porphobilinogen deaminase (PBGD) mRNA, targeting the liver, demonstrated its efficacy and safety to replace the defective PBGD protein in preclinical models of acute intermittent porphyria.
|
30528119 |
2019 |
|
Acute intermittent porphyria
|
1.000 |
Biomarker
|
disease |
BEFREE |
Acute intermittent porphyria (AIP) is a low-penetrant genetic metabolic disease caused by a deficiency of hydroxymethylbilane synthase (HMBS) in the haem biosynthesis.
|
30808393 |
2019 |
|
Acute intermittent porphyria
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
These studies identified novel pathogenic HMBS mutations and expanded the molecular heterogeneity of AIP.
|
30740734 |
2019 |
|
Acute intermittent porphyria
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
Here, we characterized the reactivity of mesenteric arteries from male and female AIP mice with ~30% of normal PBGD activity and wild type C57BL/6 mice.
|
30639047 |
2019 |
|
Acute intermittent porphyria
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Molecular genetic study of acute intermittent porphyria in Russia: HMBS gene mutation spectrum and problem of penetrance.
|
31044425 |
2019 |
|
Acute intermittent porphyria
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Acute Intermittent Porphyria (AIP), an autosomal dominant hepatic disorder, results from hydroxymethylbilane synthase (HMBS) mutations that decrease the encoded enzymatic activity, thereby predisposing patients to life-threatening acute neurovisceral attacks.
|
30777612 |
2019 |
|
Acute intermittent porphyria
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Mice with severe HMBS deficiency, which clinically and biochemically mimic the early-onset homozygous dominant AIP (HD-AIP) patients, have been generated and were used to elucidate the striking phenotypic differences between AIP and HD-AIP.
|
30737139 |
2019 |
|
Acute intermittent porphyria
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
To better interpret the underlying mechanism of clinical phenotypes, we collected 117 <i>HMBS</i> gene mutations from reported individuals with AIP and evaluated the mutations' impacts on the corresponding protein structure and function.
|
31572191 |
2019 |
|
Acute intermittent porphyria
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Acute intermittent porphyria (AIP) is an inherited metabolic disease with low clinical penetrance caused by mutations in the hydroxymethylbilane (HMBS) gene.
|
31269991 |
2019 |
|
Acute intermittent porphyria
|
1.000 |
Biomarker
|
disease |
BEFREE |
Acute intermittent porphyria (AIP) is an inherited disorder of haem metabolism characterized by life-threatening acute neurovisceral attacks due to the induction of hepatic δ-aminolevulinic acid synthase 1 (ALAS1) associated with hydroxymethylbilane synthase (HMBS) deficiency.
|
29498764 |
2018 |
|
Acute intermittent porphyria
|
1.000 |
Biomarker
|
disease |
BEFREE |
Molecular characterization, by digital PCR analysis of four HMBS gene mutations affecting the ubiquitous isoform of Porphobilinogen Deaminase (PBGD) in patients with Acute Intermittent Porphyria (AIP).
|
30201327 |
2018 |
|
Acute intermittent porphyria
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
PBG-D activity was further reduced by Isoflurane in liver male T1; in AIP male mice activity remained in its low basal levels.
|
29476795 |
2018 |
|
Acute intermittent porphyria
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
A novel 55-basepair deletion of hydroxymethylbilane synthase gene found in a Chinese patient with acute intermittent porphyria and her family: A case report.
|
30212967 |
2018 |
|
Acute intermittent porphyria
|
1.000 |
Biomarker
|
disease |
BEFREE |
Acute intermittent porphyria (AIP) results from haploinsufficiency of porphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthesis pathway.
|
30297912 |
2018 |
|
Acute intermittent porphyria
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
The three groups of subjects were used to establish the best cut-off of PBGD activity for identifying symptomatic AIP patients by using area under receiver operating characteristic curve analysis.
|
29317194 |
2018 |
|
Acute intermittent porphyria
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
In conclusion, the striking difference in the penetrance of HMBS mutations between the general population and the French AIP families suggests that AIP inheritance does not follow the classical autosomal dominant model, instead of being modulated by strong environmental and genetic factors independent from HMBS.
|
29360981 |
2018 |
|
Acute intermittent porphyria
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
Acute intermittent porphyria (AIP) is a heme pathway disorder caused by a decrease in the activity and synthesis of porphobilinogen deaminase.
|
30218352 |
2018 |
|
Acute intermittent porphyria
|
1.000 |
Biomarker
|
disease |
BEFREE |
Mutations in human <i>HMBS</i> (<i>hHMBS</i>) cause acute intermittent porphyria (AIP), an autosomal-dominant disorder characterized by life-threatening neurovisceral attacks.
|
29632172 |
2018 |
|
Acute intermittent porphyria
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Finally, full protection against a phenobarbital-induced attack was achieved in AIP mice after the administration of 1 × 1011 gc/kg of rAAV2/8-PBGD-I291M/N340S vector; three times lower than the dose required to achieve full protection with the control rAAV2/8-hPBGD vector.
|
30085095 |
2018 |
|
Acute intermittent porphyria
|
1.000 |
Biomarker
|
disease |
BEFREE |
Porphobilinogen deaminase (PBGD) gene therapy represents a promising therapeutic option for acute intermittent porphyria (AIP) patients suffering recurrent acute attacks.
|
28990424 |
2018 |
|
Acute intermittent porphyria
|
1.000 |
Biomarker
|
disease |
BEFREE |
Acute intermittent porphyria (AIP) is a rare metabolic disorder due to a deficiency of porphobilinogen deaminase, the third enzyme of the heme biosynthetic pathway.
|
28666226 |
2017 |
|
Acute intermittent porphyria
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Establishing accurate diagnoses of the patient and asymptomatic family members with AIP involves identifying the PBGD enzyme mutations directly.
|
28011390 |
2017 |
|
Acute intermittent porphyria
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Acute intermittent porphyria (AIP) is a disorder of the haem biosynthetic pathway caused by mutations in the hydroxymethylbilane synthase (<i>HMBS</i>) gene.
|
27849156 |
2017 |