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Novel PRMT7 mutation in a rare case of dysmorphism and intellectual disability

Journal of Human Genetics volume 67, pages 19–26 (2022)Cite this article

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Abstract

Protein arginine N-methyltransferase 7 (PRMT7) encodes an arginine methyltransferase central to a number of fundamental biological processes, mutations in which result in an autosomal recessive developmental disorder characterized by short stature, brachydactyly, intellectual developmental disability and seizures (SBIDDS). To date, fewer than 15 patients with biallelic mutations in PRMT7 have been documented. Here we report brothers from a consanguineous Iraqi family presenting with a developmental disorder characterized by global developmental delay, shortened stature, facial dysmorphisms, brachydactyly, and kidney dysfunction. In both affected brothers, whole genome sequencing (WGS) identified a novel homozygous substitution in PRMT7 (ENST00000339507.5), c.1097 G > A (p.Cys366Tyr), considered to account for the majority of the phenotypic presentation. Rare compound heterozygous mutations in the dysplasia-associated perlecan-encoding HSPG2 gene (ENST00000374695.3) were also found (c.10721-2dupA, p.Ser71Asn and c.212 G > A), potentially accounting for the kidney dysfunction. In addition to expanding the known mutational spectrum of variably expressive PRMT7 mutations alongside potential digenic inheritance with HSPG2, this report underlines the diagnostic utility of a WGS-guided analysis in the detection of rare genetic disorders.

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Acknowledgements

The families are gratefully acknowledged for their participation in the study. The study was supported by the New Zealand eScience Infrastructure.

Funding

JCJ is supported by a government-funded Rutherford Discovery Fellowship administered by the Royal Society of New Zealand. The research was funded by the IHC Foundation.

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Authors and Affiliations

  1. School of Biological Sciences, The University of Auckland, Auckland, New Zealand

    Jessie Poquérusse, Whitney Whitford, Russell G. Snell, Klaus Lehnert & Jessie C. Jacobsen

  2. Centre for Brain Research, The University of Auckland, Auckland, New Zealand

    Jessie Poquérusse, Whitney Whitford, Russell G. Snell, Klaus Lehnert & Jessie C. Jacobsen

  3. Genetic Health Service New Zealand, Auckland City Hospital, Auckland, New Zealand

    Juliet Taylor & Salam Alburaiky

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  1. Jessie Poquérusse
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Contributions

JCJ, KL and RGS conceived the experiments. JP and WW performed DNA-based laboratory experiments. JP, WW, KL, RGS and JCJ performed data and bioinformatic analysis. JT and SA conducted the clinical evaluation. JP and JCJ wrote the paper. All authors reviewed the paper.

Corresponding author

Correspondence to Jessie C. Jacobsen.

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Ethical approval

Ethical approval was obtained by the Northern B Health and Disability Ethics Committee (12/NTB/59) prior to acquiring, sequencing, and analyzing all human genetic information. All procedures were performed in accordance with the ethical standards of the institutional and national responsible committees on human experimentation and with the 1975 Helsinki Declaration (as revised in 2000).

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Consent was obtained from the patient’s family for publication of this report.

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The authors declare no competing interests.

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Poquérusse, J., Whitford, W., Taylor, J. et al. Novel PRMT7 mutation in a rare case of dysmorphism and intellectual disability. J Hum Genet 67, 19–26 (2022). https://doi.org/10.1038/s10038-021-00955-5

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