title: Congenital erythropoietic porphyria linked to GATA1-R216W mutation: challenges for diagnosis.
abstract: Congenital erythropoietic porphyria (CEP) is a rare genetic disease that is characterized by a severe cutaneous photosensitivity causing unrecoverable deformities, chronic hemolytic anemia requiring blood transfusion program, and by fatal systemic complications. A correct and early diagnosis is required to develop a management plan that is appropriate to the patient's needs. Recently only one case of X-linked CEP had been reported, describing the trans-acting GATA1-R216W mutation. Here, we have characterized two novel X-linked CEP patients, both with misleading hematological phenotypes that include dyserythropoietic anemia, thrombocytopenia, and hereditary persistence of fetal hemoglobin. We compare the previously reported case to ours and propose a diagnostic paradigm for this variant of CEP. Finally, a correlation between phenotype variability and the presence of modifier mutations in loci related to disease-causing gene is described.
authors.affiliation: Fondazione IRCCS "Cà-Granda" Ospedale Maggiore Policlinico, U.O. di Medicina Interna, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Di Pierro
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Naples, Italy.|CEINGE - Biotecnologie Avanzate, Naples, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Russo
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Karakas
authors.affiliation: Fondazione IRCCS "Cà-Granda" Ospedale Maggiore Policlinico, U.O. di Medicina Interna, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Brancaleoni
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Naples, Italy.|CEINGE - Biotecnologie Avanzate, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Gambale
authors.affiliation: Department of Biochemistry and Clinical Biochemistry - Laboratory of Porphiria, Gulhane Military Academy of Medicine, Ankara, Turkey.
authors.forename: Ismail
authors.initials: I
authors.lastname: Kurt
authors.affiliation: Department of Pediatrics, University of New Mexico, Albuquerque, NM, USA.
authors.forename: S Stuart
authors.initials: SS
authors.lastname: Winter
authors.affiliation: Fondazione IRCCS "Cà-Granda" Ospedale Maggiore Policlinico, U.O. di Medicina Interna, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Granata
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: David Rodriguez
authors.initials: DR
authors.lastname: Czuchlewski
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Naples, Italy.|CEINGE - Biotecnologie Avanzate, Naples, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Langella
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Naples, Italy.|CEINGE - Biotecnologie Avanzate, Naples, Italy.
authors.forename: Achille
authors.initials: A
authors.lastname: Iolascon
authors.affiliation: Fondazione IRCCS "Cà-Granda" Ospedale Maggiore Policlinico, U.O. di Medicina Interna, Milan, Italy.|Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Milan, Italy.
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
mesh_terms: D019943:Amino Acid Substitution; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004909:Erythrocyte Indices; D050982:GATA1 Transcription Factor / Q000235:genetics*; D050172:Genes, X-Linked; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017092:Porphyria, Erythropoietic / Q000175:diagnosis* / Q000235:genetics*; D011166:Porphyrins / Q000097:blood / Q000652:urine
chemical_list: D050982:GATA1 Transcription Factor; D011166:Porphyrins
keywords: UROS, GATA1, and SEC23B mutations; congenital erythropoietic porphyria; neonatal hemolytic anemia