Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
1.
Am J Hum Genet ; 97(1): 163-9, 2015 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-26073778

RESUMEN

Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency. Few conditions are known to cause recurrent acute liver failure (RALF), and in about 50% of cases, the underlying molecular cause remains unresolved. Exome sequencing in five unrelated individuals with fever-dependent RALF revealed biallelic mutations in NBAS. Subsequent Sanger sequencing of NBAS in 15 additional unrelated individuals with RALF or ALF identified compound heterozygous mutations in an additional six individuals from five families. Immunoblot analysis of mutant fibroblasts showed reduced protein levels of NBAS and its proposed interaction partner p31, both involved in retrograde transport between endoplasmic reticulum and Golgi. We recommend NBAS analysis in individuals with acute infantile liver failure, especially if triggered by fever.


Asunto(s)
Fallo Hepático Agudo/genética , Proteínas de Neoplasias/genética , Secuencia de Bases , Transporte Biológico/genética , Exoma/genética , Fibroblastos/metabolismo , Frecuencia de los Genes , Alemania , Humanos , Immunoblotting , Lactante , Datos de Secuencia Molecular , Proteínas de Neoplasias/metabolismo , Linaje , Recurrencia , Análisis de Secuencia de ADN
2.
J Inherit Metab Dis ; 39(1): 3-16, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26541327

RESUMEN

BACKGROUND: Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency and in about 50% the etiology remains unknown. Recently biallelic mutations in NBAS were identified as a new molecular cause of ALF with onset in infancy, leading to recurrent acute liver failure (RALF). METHODS: The phenotype and medical history of 14 individuals with NBAS deficiency was studied in detail and functional studies were performed on patients' fibroblasts. RESULTS: The phenotypic spectrum of NBAS deficiency ranges from isolated RALF to a multisystemic disease with short stature, skeletal dysplasia, immunological abnormalities, optic atrophy, and normal motor and cognitive development resembling SOPH syndrome. Liver crises are triggered by febrile infections; they become less frequent with age but are not restricted to childhood. Complete recovery is typical, but ALF crises can be fatal. Antipyretic therapy and induction of anabolism including glucose and parenteral lipids effectively ameliorates the course of liver crises. Patients' fibroblasts showed an increased sensitivity to high temperature at protein and functional level and a disturbed tethering of vesicles, pointing at a defect of intracellular transport between the endoplasmic reticulum and Golgi. CONCLUSIONS: Mutations in NBAS cause a complex disease with a wide clinical spectrum ranging from isolated RALF to a multisystemic phenotype. Thermal susceptibility of the syntaxin 18 complex is the basis of fever dependency of ALF episodes. NBAS deficiency is the first disease related to a primary defect of retrograde transport. Identification of NBAS deficiency allows optimized therapy of liver crises and even prevention of further episodes.


Asunto(s)
Fallo Hepático Agudo/genética , Fallo Hepático Agudo/patología , Proteínas de Neoplasias/deficiencia , Adolescente , Adulto , Niño , Preescolar , Femenino , Fibroblastos/patología , Humanos , Lactante , Hígado/patología , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Masculino , Mutación/genética , Fenotipo , Recurrencia , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA