ABSTRACT
Adverse drug reactions occur at a high rate in hospitalized children, frequently due to antiepileptic drug administration. Phenytoin is a commonly used drug, and its metabolism is mediated by a specific cytochrome-P450 isoform, CYP2C9, which is encoded by a polymorphic gene. It is worth noting that very frequently administered drugs, such as proton pump inhibitors, compete with phenytoin for CYP2C19-mediated metabolism. Here we describe a case of phenytoin intoxication in a child with defective CYP2C9, after omeprazole administration.
Subject(s)
Cytochrome P-450 CYP2C9/metabolism , Omeprazole/administration & dosage , Phenytoin/adverse effects , Child, Preschool , Cytochrome P-450 CYP2C19/metabolism , Cytochrome P-450 CYP2C9/genetics , Drug Interactions , Genotype , Humans , Phenytoin/blood , Polymorphism, GeneticSubject(s)
Acne Vulgaris/genetics , Agenesis of Corpus Callosum/genetics , Orofaciodigital Syndromes/genetics , Proteins/genetics , Acne Vulgaris/etiology , Agenesis of Corpus Callosum/diagnostic imaging , Agenesis of Corpus Callosum/etiology , Female , Frameshift Mutation , Humans , Infant , Lateral Ventricles/abnormalities , Lateral Ventricles/diagnostic imaging , Orofaciodigital Syndromes/complications , Orofaciodigital Syndromes/diagnosisABSTRACT
The original version of this article contained a mistake in the affiliation of E. Bellacchio. Correct affiliation is presented here.
ABSTRACT
Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyze the transfer of methyl groups from S-adenosyl-l-methionine to nitrogen atoms on arginine residues. Arginine methylation is involved in multiple biological processes, such as signal transduction, mRNA splicing, transcriptional control, DNA repair, and protein translocation. Currently, 7 patients have been described harboring compound heterozygous or homozygous variants in the PRMT7 gene, causing a novel intellectual disability syndrome, known as SBIDDS syndrome (Short Stature, Brachydactyly, Intellectual Developmental Disability, and Seizures). We report on 3 additional patients from 2 consanguineous families with severe/moderate intellectual disability, short stature, brachydactyly and dysmorphisms. Exome sequencing revealed 2 novel homozygous mutations in PRMT7. Our findings expand the clinical and molecular spectrum of homozygous PRMT7 mutations, associated to the SBIDDS syndrome, showing a possible correlation between the type of mutation and the severity of the phenotype.
Subject(s)
Genetic Association Studies , Genetic Predisposition to Disease , Mutation , Phenotype , Protein-Arginine N-Methyltransferases/genetics , Adolescent , Alleles , Comparative Genomic Hybridization , Consanguinity , Female , Genetic Association Studies/methods , Genotype , Humans , Karyotype , Male , Pedigree , Radiography , Young AdultSubject(s)
Exons/genetics , Membrane Proteins/genetics , Mutation/genetics , Wolfram Syndrome/genetics , Amino Acid Sequence , Base Sequence , Child , Child, Preschool , Family , Female , Homozygote , Humans , Italy , Male , Membrane Proteins/chemistry , Molecular Sequence Data , Pedigree , Young AdultABSTRACT
Cleft Lip/Palate-Ectodermal Dysplasia and Ectodermal Dysplasia-Syndactyly Syndrome are rare congenital disorders caused by recessive mutations in the PVRL1 and PVRL4 genes, respectively. These genes encode nectins 1 and 4, an emerging class of molecules acting in cooperation with cadherins to form cell-cell adhesion especially at adherens junctions. Their role in skin, hair and teeth biology and in the fine-tuning morphogenesis of craniofacial (lip/palate) and limbs is yet to be outlined prompting future research. We propose refer to these entities (nectin 1-ED and nectin 4-ED) as "nectinopathies", which are likely to be underestimated/underdiagnosed ED syndomes.
