RESUMO
Otofaciocervical syndrome (OFCS) is a rare disorder characterized by facial anomalies, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies, and mild intellectual disability. Autosomal dominant cases are caused by deletions or point mutations of EYA1. A single family with an autosomal recessive form of OFCS and a homozygous missense mutation in PAX1 gene has been described. We report whole exome sequencing of 4 members of a consanguineous family in which 2 children, showing features of OFCS, expired from severe combined immunodeficiency (SCID). To date, the co-occurrence of OFCS and SCID has never been reported. We found a nonsense homozygous mutation in PAX1 gene in the 2 affected children. In mice, Pax1 is required for the formation of specific skeletal structures as well as for the development of a fully functional thymus. The mouse model strongly supports the hypothesis that PAX1 depletion in our patients caused thymus aplasia responsible for SCID. This report provides evidence that bi-allelic null PAX1 mutations may lead to a multi-system autosomal recessive disorders, where SCID might represent the main feature.
Assuntos
Síndrome Brânquio-Otorrenal/genética , Deficiência Intelectual/genética , Mutação , Fatores de Transcrição Box Pareados/genética , Imunodeficiência Combinada Severa/genética , Animais , Sequência de Bases , Síndrome Brânquio-Otorrenal/complicações , Síndrome Brânquio-Otorrenal/imunologia , Síndrome Brânquio-Otorrenal/patologia , Criança , Consanguinidade , Modelos Animais de Doenças , Exoma , Família , Feminino , Expressão Gênica , Genes Recessivos , Humanos , Lactente , Deficiência Intelectual/complicações , Deficiência Intelectual/imunologia , Deficiência Intelectual/patologia , Masculino , Camundongos , Marrocos , Fatores de Transcrição Box Pareados/imunologia , Linhagem , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/patologia , Timo/anormalidades , Timo/imunologia , Timo/metabolismoRESUMO
A novel class I human leukocyte antigen allele HLA-A*24:309 is described.
Assuntos
Alelos , Medula Óssea , Antígenos HLA-A/genética , Doadores de Tecidos , Humanos , Itália , MasculinoRESUMO
A newly identified allele, named HLA-DRB1*13:154, differs from DRB1*13:13 by the single nucleotide substitution 227T-A at codon 47 in exon 2.
