Studies on the clinical manifestation and SLC25A13 gene mutation of Chinese patients with neonatal intrahepatic cholestasis caused by citrin deficiency / 中华医学遗传学杂志
Chinese Journal of Medical Genetics
;
(6): 180-185, 2010.
Artículo
en Chino
| WPRIM
| ID: wpr-349016
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinical and laboratory features of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and to characterize the molecular basis and prognosis of this disease.</p><p><b>METHODS</b>Twenty-six patients with NICCD were collected because of idiopathic intrahepatic cholestasis and jaundice. The diagnosis was made by routine laboratory data collection, tandem mass spectrometry (MS-MS) and gas chromatography mass spectrometry (GC-MS) analyses. SLC25A13 gene mutation was analyzed by using polymerase chain reaction (PCR), direct DNA sequencing and restriction fragment length polymorphism analyses. The patients were followed up for nearly 2 years.</p><p><b>RESULTS</b>The NICCD patients showed low birth weight and the average onset of jaundice was 29 days. Laboratory data showed liver dysfunction, hyperbilirubinemia, hypoproteinemia, high levels of alpha-fetoprotein, prolonged prothrombin time, hypoglycemia and hyperammonemia. MS-MS analysis of the blood samples revealed specific elevation of citrulline, methionine, threonine, tyrosine and elevation of free carnitine, short-chain and long-chain acylcarnitines. GC-MS analysis of the urine samples showed elevated 4-hydroxyl phenyllactic acid and 4-hydroxyl phenylpyruvic acid. Twelve different mutations were identified, including 4 novel mutations, i.e., G386V, R467X, K453R and 1192-1193delT. Forty-four mutated alleles were identified in the 52 alleles (84.6% ). Among them, 851del4, 1638ins23 and IVS6+5G>A mutations were the most frequent mutations, accounting for 40.9%, 20.5% and 11.4% of the total alleles examined respectively. Five of the 26 patients have not been recovered, including 4 died and 1 accepted liver transplantation. No obvious relationship was found between the genotype and phenotype in NICCD.</p><p><b>CONCLUSION</b>The 851del4, 1638ins23 and IVS6+5G>A mutations are the hot-spot mutations in Chinese NICCD patients. Some NICCD patients have poor prognosis.</p>
Texto completo:
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Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Pronóstico
/
Terapéutica
/
Proteínas de Unión al Calcio
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Análisis Mutacional de ADN
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Secuencia de Bases
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Estudios de Casos y Controles
/
Colestasis Intrahepática
/
Estudios de Seguimiento
/
Progresión de la Enfermedad
/
Transportadores de Anión Orgánico
Tipo de estudio:
Estudio diagnóstico
/
Estudio observacional
/
Estudio pronóstico
Límite:
Child, preschool
/
Humanos
/
Lactante
/
Masculino
/
Recién Nacido
Idioma:
Chino
Revista:
Chinese Journal of Medical Genetics
Año:
2010
Tipo del documento:
Artículo
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