RESUMO
Understanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge of key transcriptional regulators has predominantly come from mouse studies, with rare, naturally occurring mutations establishing their relevance in man. This study used a combination of homozygosity analysis and Sanger sequencing in 37 consanguineous patients with permanent neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development. We identified homozygous mutations in 7 different genes in 11 unrelated patients and show that NKX2-2 and MNX1 are etiological genes for neonatal diabetes, thus confirming their key role in development of the human pancreas. The similar phenotype of the patients with recessive mutations and mice with inactivation of a transcription factor gene support there being common steps critical for pancreatic development and validate the use of rodent models for beta cell development.
Assuntos
Diabetes Mellitus/genética , Proteínas de Homeodomínio/genética , Mutação/genética , Pâncreas/crescimento & desenvolvimento , Pâncreas/metabolismo , Fatores de Transcrição/genética , Adolescente , Sequência de Aminoácidos , Animais , Pré-Escolar , Diabetes Mellitus/patologia , Feminino , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodomínio/química , Homozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Camundongos , Dados de Sequência Molecular , Proteínas Nucleares , Fenótipo , Fatores de Transcrição/química , Proteínas de Peixe-ZebraRESUMO
Respiratory distress in a moderately preterm baby often presents diagnostic and management challenges to the attending paediatrician. Many of these babies will require little or no intervention, but it is known that early intervention in babies with acute respiratory distress often prevents further complications. Most current research evidence relates to extremely preterm newborns, yet moderately preterm infants are numerically far more common. This article explores the differential diagnosis of respiratory distress in this population and presents an evidence based approach to treatment.