Tags

Type your tag names separated by a space and hit enter

Hepatoerythropoietic Porphyria Caused by a Novel Homoallelic Mutation in Uroporphyrinogen Decarboxylase Gene in Egyptian Patients.
Folia Biol (Praha). 2015; 61(6):219-26.FB

Abstract

Porphyrias are metabolic disorders resulting from mutations in haem biosynthetic pathway genes. Hepatoerythropoietic porphyria (HEP) is a rare type of porphyria caused by the deficiency of the fifth enzyme (uroporphyrinogen decarboxylase, UROD) in this pathway. The defect in the enzymatic activity is due to biallelic mutations in the UROD gene. Currently, 109 UROD mutations are known. The human disease has an early onset, manifesting in infancy or early childhood with red urine, skin photosensitivity in sun-exposed areas, and hypertrichosis. Similar defects and links to photosensitivity and hepatopathy exist in several animal models, including zebrafish and mice. In the present study, we report a new mutation in the UROD gene in Egyptian patients with HEP. We show that the homozygous c.T163A missense mutation leads to a substitution of a conserved phenylalanine (amino acid 55) for isoleucine in the enzyme active site, causing a dramatic decrease in the enzyme activity (19 % of activity of wild-type enzyme). Inspection of the UROD crystal structure shows that Phe-55 contacts the substrate and is located in the loop that connects helices 2 and 3. Phe-55 is strictly conserved in both prokaryotic and eukaryotic UROD. The F55I substitution likely interferes with the enzyme-substrate interaction.

Authors+Show Affiliations

Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.University of Bordeaux, Bordeaux, France.University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.University of Bordeaux, Bordeaux, France.Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26789143

Citation

Farrag, M S., et al. "Hepatoerythropoietic Porphyria Caused By a Novel Homoallelic Mutation in Uroporphyrinogen Decarboxylase Gene in Egyptian Patients." Folia Biologica, vol. 61, no. 6, 2015, pp. 219-26.
Farrag MS, Mikula I, Richard E, et al. Hepatoerythropoietic Porphyria Caused by a Novel Homoallelic Mutation in Uroporphyrinogen Decarboxylase Gene in Egyptian Patients. Folia Biol (Praha). 2015;61(6):219-26.
Farrag, M. S., Mikula, I., Richard, E., Saudek, V., De Verneuil, H., & Martásek, P. (2015). Hepatoerythropoietic Porphyria Caused by a Novel Homoallelic Mutation in Uroporphyrinogen Decarboxylase Gene in Egyptian Patients. Folia Biologica, 61(6), 219-26.
Farrag MS, et al. Hepatoerythropoietic Porphyria Caused By a Novel Homoallelic Mutation in Uroporphyrinogen Decarboxylase Gene in Egyptian Patients. Folia Biol (Praha). 2015;61(6):219-26. PubMed PMID: 26789143.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatoerythropoietic Porphyria Caused by a Novel Homoallelic Mutation in Uroporphyrinogen Decarboxylase Gene in Egyptian Patients. AU - Farrag,M S, AU - Mikula,I, AU - Richard,E, AU - Saudek,V, AU - De Verneuil,H, AU - Martásek,P, PY - 2016/1/21/entrez PY - 2016/1/21/pubmed PY - 2016/10/19/medline SP - 219 EP - 26 JF - Folia biologica JO - Folia Biol (Praha) VL - 61 IS - 6 N2 - Porphyrias are metabolic disorders resulting from mutations in haem biosynthetic pathway genes. Hepatoerythropoietic porphyria (HEP) is a rare type of porphyria caused by the deficiency of the fifth enzyme (uroporphyrinogen decarboxylase, UROD) in this pathway. The defect in the enzymatic activity is due to biallelic mutations in the UROD gene. Currently, 109 UROD mutations are known. The human disease has an early onset, manifesting in infancy or early childhood with red urine, skin photosensitivity in sun-exposed areas, and hypertrichosis. Similar defects and links to photosensitivity and hepatopathy exist in several animal models, including zebrafish and mice. In the present study, we report a new mutation in the UROD gene in Egyptian patients with HEP. We show that the homozygous c.T163A missense mutation leads to a substitution of a conserved phenylalanine (amino acid 55) for isoleucine in the enzyme active site, causing a dramatic decrease in the enzyme activity (19 % of activity of wild-type enzyme). Inspection of the UROD crystal structure shows that Phe-55 contacts the substrate and is located in the loop that connects helices 2 and 3. Phe-55 is strictly conserved in both prokaryotic and eukaryotic UROD. The F55I substitution likely interferes with the enzyme-substrate interaction. SN - 0015-5500 UR - https://www.unboundmedicine.com/medline/citation/26789143/Hepatoerythropoietic_Porphyria_Caused_by_a_Novel_Homoallelic_Mutation_in_Uroporphyrinogen_Decarboxylase_Gene_in_Egyptian_Patients_ L2 - https://fb.cuni.cz/volume-61-2015-no-6#articFB2015A0028 DB - PRIME DP - Unbound Medicine ER -