Point Mutations in the Uroporphyrinogen III Synthase Gene in Congenital Erythropoietic Porphyria (G�nther�s Disease)

2015 ◽  
pp. 148-153 ◽  
Author(s):  
Yves Nordmann ◽  
Jean-Charles Deybach ◽  
Hubert de Verneuil ◽  
Samia Boulechfar ◽  
Bernard Grandchamp
Keyword(s):  
Point Mutations ◽  
Congenital Erythropoietic Porphyria

scholarly journals Point mutations in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria (Gunther's disease)

Blood ◽  
1990 ◽  
Vol 75 (9) ◽  
pp. 1763-1765 ◽  
Author(s):  
JC Deybach ◽  
H de Verneuil ◽  
S Boulechfar ◽  
B Grandchamp ◽  
Y Nordmann
Keyword(s):  
Polymerase Chain Reaction ◽  
Autosomal Recessive ◽  
Distinct Point ◽  
Point Mutations ◽  
Chain Reaction ◽  
Complementary Dna ◽  
Congenital Erythropoietic Porphyria ◽  
Molecular Abnormality ◽  
Allele Specific ◽  
Polymerase Chain

Congenital erythropoietic porphyria (Gunther's disease) is a rare disorder of heme biosynthesis inherited in an autosomal recessive fashion. The molecular abnormality responsible for the characteristic defect in uroporphyrinogen III synthase activity was investigated in two patients. For the first patient, complementary DNA was specifically amplified using the polymerase chain reaction and subsequently cloned and sequenced. Data obtained revealed the coexistence of two distinct point mutations: a T to C change in codon 73 (arginine in place of a cysteine) and a C to T change in codon 53 (leucine in place of a proline). The second case was studied by hybridization with allele specific oligonucleotides and was found to be homozygous for the same mutation in codon 53. These are the first mutations to be recognized in the uroporphyrinogen III synthase gene from congenital erythropoietic porphyria patients.

scholarly journals Metabolic correction of congenital erythropoietic porphyria by retrovirus-mediated gene transfer into Epstein-Barr virus-transformed B- cell lines

Blood ◽  
1995 ◽  
Vol 85 (6) ◽  
pp. 1449-1453 ◽  
Author(s):  
F Moreau-Gaudry ◽  
F Mazurier ◽  
M Bensidhoum ◽  
C Ged ◽  
H de Verneuil
Keyword(s):  
Gene Therapy ◽  
B Cell ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Age Of Onset ◽  
Point Mutations ◽  
Barr Virus ◽  
Congenital Erythropoietic Porphyria ◽  
Epstein Barr ◽  
Metabolic Correction

Congenital erythropoietic porphyria (CEP) is an inherited metabolic disorder resulting from the accumulation of porphyrins because of defective uroporphyrinogen III synthase (UROIIIS). This autosomal recessive disorder is phenotypically heterogeneous with respect to the age of onset and the severity of the symptoms. Different exonic point mutations in the UROIIIS gene have been identified, providing phenotype- genotype correlations in this disease. Severe cases may be treated by bone marrow transplantation and are potential candidates for somatic gene therapy. Epstein-Barr virus-transformed B-cell lines from patients with CEP provide a model system for the disease. We have used retrovirus-mediated expression of UROIIIS to restore enzymatic activity in a B-cell line from a patient. We have also demonstrated the metabolic correction of the disease, ie, porphyrin accumulation into the deficient transduced cells was reduced to the normal level. These data show the potential of gene therapy for this disease.

scholarly journals Point mutations in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria (Gunther's disease)

Blood ◽  
1990 ◽  
Vol 75 (9) ◽  
pp. 1763-1765 ◽  
Author(s):  
JC Deybach ◽  
H de Verneuil ◽  
S Boulechfar ◽  
B Grandchamp ◽  
Y Nordmann
Keyword(s):  
Polymerase Chain Reaction ◽  
Autosomal Recessive ◽  
Distinct Point ◽  
Point Mutations ◽  
Chain Reaction ◽  
Complementary Dna ◽  
Congenital Erythropoietic Porphyria ◽  
Molecular Abnormality ◽  
Allele Specific ◽  
Polymerase Chain

Abstract Congenital erythropoietic porphyria (Gunther's disease) is a rare disorder of heme biosynthesis inherited in an autosomal recessive fashion. The molecular abnormality responsible for the characteristic defect in uroporphyrinogen III synthase activity was investigated in two patients. For the first patient, complementary DNA was specifically amplified using the polymerase chain reaction and subsequently cloned and sequenced. Data obtained revealed the coexistence of two distinct point mutations: a T to C change in codon 73 (arginine in place of a cysteine) and a C to T change in codon 53 (leucine in place of a proline). The second case was studied by hybridization with allele specific oligonucleotides and was found to be homozygous for the same mutation in codon 53. These are the first mutations to be recognized in the uroporphyrinogen III synthase gene from congenital erythropoietic porphyria patients.

A Novel Mutation Glyl672→Arg in Type 2A and a Homozygous Mutation in Type 2B von Willebrand Disease

1996 ◽  
Vol 76 (02) ◽  
pp. 253-257 ◽  
Author(s):  
Takeshi Hagiwara ◽  
Hiroshi Inaba ◽  
Shinichi Yoshida ◽  
Keiko Nagaizumi ◽  
Morio Arai ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Novel Mutation ◽  
Point Mutations ◽  
Japanese Patients ◽  
Von Willebrand Disease ◽  
Homozygous Mutation ◽  
Missense Mutations ◽  
Reaction Products ◽  
Type 3 ◽  
Von Willebrand

SummaryGenetic materials from 16 unrelated Japanese patients with von Willebrand disease (vWD) were analyzed for mutations. Exon 28 of the von Willebrand factor (vWF) gene, where point mutations have been found most frequent, was screened by various restriction-enzyme analyses. Six patients were observed to have abnormal restriction patterns. By sequence analyses of the polymerase chain-reaction products, we identified a homozygous R1308C missense mutation in a patient with type 2B vWD; R1597W, R1597Q, G1609R and G1672R missense mutations in five patients with type 2A; and a G1659ter nonsense mutation in a patient with type 3 vWD. The G1672R was a novel missense mutation of the carboxyl-terminal end of the A2 domain. In addition, we detected an A/C polymorphism at nucleotide 4915 with HaeIII. There was no particular linkage disequilibrium of the A/C polymorphism, either with the G/A polymorphism at nucleotide 4391 detected with Hphl or with the C/T at 4891 detected with BstEll.

PREVALENCE OF COMMON MITOCHONDRIAL POINT MUTATIONS IN AUTISM

2006 ◽  
Vol 37 (S 1) ◽  
Author(s):  
FJ Serajee ◽  
H Zhong ◽  
AHMM Huq
Keyword(s):  
Point Mutations

Cupin Variants as Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

2019 ◽  
Author(s):  
Nobutaka Fujieda ◽  
Miho Yuasa ◽  
Yosuke Nishikawa ◽  
Genji Kurisu ◽  
Shinobu Itoh ◽  
...  
Keyword(s):  
Michael Addition ◽  
In Silico ◽  
Addition Reaction ◽  
Single Point ◽  
Point Mutations ◽  
Unsaturated Ketone ◽  
Michael Addition Reaction ◽  
Beta Barrel ◽  
Cupin Superfamily ◽  
Single Point Mutations

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantio-selective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, in silico substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.

The Impact of Bioconjugation on the Interfacial Activity of a Protein Biosurfactant

2018 ◽  
Author(s):  
Hossam H Tayeb ◽  
Marina Stienecker ◽  
Anton Middelberg ◽  
Frank Sainsbury
Keyword(s):  
Polyethylene Glycol ◽  
Colloidal Stability ◽  
Point Mutations ◽  
Pharmaceutical Formulations ◽  
Industrial Processes ◽  
Parent Molecule ◽  
Site Specific ◽  
Interfacial Activity ◽  
Surface Active ◽  
The Impact

Biosurfactants, are surface active molecules that can be produced by renewable, industrially scalable biologic processes. DAMP4, a designer biosurfactant, enables the modification of interfaces via genetic or chemical fusion to functional moieties. However, bioconjugation of addressable amines introduces heterogeneity that limits the precision of functionalization as well as the resolution of interfacial characterization. Here we designed DAMP4 variants with cysteine point mutations to allow for site-specific bioconjugation. The DAMP4 variants were shown to retain the structural stability and interfacial activity characteristic of the parent molecule, while permitting efficient and specific conjugation of polyethylene glycol (PEG). PEGylation results in a considerable reduction on the interfacial activity of both single and double mutants. Comparison of conjugates with one or two conjugation sites shows that both the number of conjugates as well as the mass of conjugated material impacts the interfacial activity of DAMP4. As a result, the ability of DAMP4 variants with multiple PEG conjugates to impart colloidal stability on peptide-stabilized emulsions is reduced. We suggest that this is due to constraints on the structure of amphiphilic helices at the interface. Specific and efficient bioconjugation permits the exploration and investigation of the interfacial properties of designer protein biosurfactants with molecular precision. Our findings should therefore inform the design and modification of biosurfactants for their increasing use in industrial processes, and nutritional and pharmaceutical formulations.

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