Journal article

Mutations in LYRM4, encoding ironsulfur cluster biogenesis factor ISD11, cause deficiency of multiple respiratory chain complexes

Sze Chern Lim, Martin Friemel, Justine E Marum, Elena J Tucker, Damien L Bruno, Lisa G Riley, John Christodoulou, Edwin P Kirk, Avihu Boneh, Christine M DeGennaro, Michael Springer, Vamsi K Mootha, Tracey A Rouault, Silke Leimkuehler, David R Thorburn, Alison G Compton

HUMAN MOLECULAR GENETICS | OXFORD UNIV PRESS | Published : 2013

Abstract

Iron-sulfur clusters (ISCs) are important prosthetic groups that define the functions of many proteins. Proteins with ISCs (called iron-sulfur or Fe-S proteins) are present in mitochondria, the cytosol, the endoplasmic reticulum and the nucleus. They participate in various biological pathways including oxidative phosphorylation (OXPHOS), the citric acid cycle, iron homeostasis, heme biosynthesis and DNA repair. Here, we report a homozygous mutation in LYRM4 in two patients with combined OXPHOS deficiency. LYRM4 encodes the ISD11 protein, which forms a complex with, and stabilizes, the sulfur donor NFS1. The homozygous mutation (c.203G>T, p.R68L) was identified via massively parallel sequenci..

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Grants

Awarded by NHLBI Lung GO Sequencing Project


Awarded by NHLBI WHI Sequencing Project


Awarded by NHLBI Broad GO Sequencing Project


Awarded by NHLBI Seattle GO Sequencing Project


Awarded by NHLBI Heart GO Sequencing Project


Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT


Funding Acknowledgements

The authors thank the NHLBI GO Exome Sequencing Project and its ongoing studies which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926) and the Heart GO Sequencing Project (HL-103010). This work was supported by a Melbourne Research Scholarship (to S. C. L.), grants and a Principal Research Fellowship from the Australian National Health and Medical Research Council (to D. R. T.), the Victorian Government's Operational Infrastructure Support Program (to D. R. T.) and support from the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (to T. A. R.), and the Deutsche Forschungsgemeinschaft (to S.L.).