Biallelic mutations in NBAS cause recurrent acute liver failure with onset in infancy

Haack, Tobias B. and Staufner, Christian and Köpke, Marlies G. and Straub, Beate K. and Kölker, Stefan and Thiel, Christian and Freisinger, Peter and Barić, Ivo and McKiernan, Patrick J. and Dikow, Nicola and Harting, Inga and Beisse, Flemming and Burgard, Peter and Kotzaeridou, Urania and Kühr, Joachim and Himbert, Urban and Taylor, Robert W. and Distelmaier, Felix and Vockley, Jerry and Ghaloul-Gonzalez, Lina and Zschocke, Johannes and Kremer, Laura S. and Graf, Elisabeth and Schwarzmayr, Thomas and Bader, Daniel M. and Gagneur, Julien and Wieland, Thomas and Terrile, Caterina and Strom, Tim M. and Meitinger, Thomas and Hoffmann, Georg F. and Prokisch, Holger (2015) Biallelic mutations in NBAS cause recurrent acute liver failure with onset in infancy. American Journal of Human Genetics, 97 (1). pp. 163-169. ISSN 0002-9297

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Abstract

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.

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