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Variable Phenotype of Severe Immunodeficiencies Associated with RMRP Gene Mutations

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Abstract

Purpose

Mutations in RMRP primarily give rise to Cartilage Hair Hypoplasia (CHH), a highly diverse skeletal disorder which can be associated with severe immunodeficiency. Increased availability of RMRP mutation screening has uncovered a number of infants with significant immunodeficiency but only mild or absent skeletal features. We surveyed the clinical and immunological phenotype of children who have undergone allogeneic haematopoietic stem cell transplantation for this condition in the UK.

Methods

Thirteen patients with confirmed RMRP mutations underwent allogeneic stem cell transplantation (SCT) at two nationally commissioned centres using a variety of donors and conditioning regimens. Records were retrospectively reviewed.

Results

Median time from clinical presentation to diagnosis was 12 months (range 1 to 276 months), with three infants diagnosed with severe combined immunodeficiency (SCID) without radiographical manifestations of CHH. A total of 17 allogeneic procedures were performed on 13 patients including two stem-cell top-ups. The median age at transplant was 32.4 months (range 1.5 to 125 months). Of the eleven surviving patients, median follow-up was 50 months (range 21.6 to 168 months).

Conclusions

RMRP mutations can cause short stature and significant immunodeficiency which can be corrected by allogeneic SCT and the diagnosis should be considered even in the absence of skeletal manifestations.

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Abbreviations

CHH:

Cartilage hair hypoplasia

RMRP:

Ribonuclease mitochondrial RNA processing

SCT:

Stem cell transplantation

SCID:

Severe combined immunodeficiency

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Acknowledgments

The authors would like to thank Kerra Pearce and Mike Hubank (UCL Genomics) for their assistance with microarrays and NGS work.

Funding Source

This work was undertaken at GOSH/UCL Institute of Child Health which received funding from the Department of Health’s NIHR Biomedical Research Centre’s funding scheme and GOSH charity special trustees. The UK service for primary immunodeficiency received support from the Department of Health via the national commissioning group (NCG).

Financial Disclosure

Winnie Ip has no financial relationships relevant to this article. All the other authors also have no financial disclosures relevant to this article.

Conflict of Interest

Winnie Ip has no conflict of interest to disclose. All the other authors also have no conflicts of interest relevant to this article to disclose.

Author information

Authors and Affiliations

  1. Molecular and Cellular Immunology Section, Institute of Child Health, University College of London, London, UK

    Winnie Ip, H. Bobby Gaspar, E. Graham Davies & Waseem Qasim

  2. Department of Clinical Immunology, Great Ormond Street Hospital, London, UK

    Winnie Ip, H. Bobby Gaspar, E. Graham Davies & Waseem Qasim

  3. Centre for Nephrology University College London, Royal Free Hospital, London, UK

    Robert Kleta

  4. Centre for Translational Omics-GOSgene, Institute of Child Health, University College, London, UK

    Estelle Chanudet & Chiara Bacchelli

  5. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK

    Alison Pitts, Zohreh Nademi, Mary A. Slatter & Andrew R. Gennery

  6. Bone Marrow Transplant Unit, Royal Victoria Infirmary, Great North Children’s Hospital, Newcastle upon Tyne, UK

    Zohreh Nademi, Mary A. Slatter & Andrew R. Gennery

  7. Bone Marrow Transplantation Department, Great Ormond Street Hospital, London, UK

    Persis Amrolia, Kanchan Rao & Paul Veys

  8. Molecular and Cellular Immunology Section, UCL Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK

    Winnie Ip

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  1. Winnie Ip
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  2. H. Bobby Gaspar
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Correspondence to Winnie Ip.

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Ip, W., Gaspar, H.B., Kleta, R. et al. Variable Phenotype of Severe Immunodeficiencies Associated with RMRP Gene Mutations. J Clin Immunol 35, 147–157 (2015). https://doi.org/10.1007/s10875-015-0135-7

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  • DOI: https://doi.org/10.1007/s10875-015-0135-7

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