Novel prmt7 mutation in a rare case of dysmorphism and intellectual disability

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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS BIALLELIC _ZNF407_ MUTATIONS IN A NEURODEVELOPMENTAL DISORDER WITH

ID, SHORT STATURE AND VARIABLE MICROCEPHALY, HYPOTONIA, OCULAR ANOMALIES AND FACIAL DYSMORPHISM Article 31 July 2020 A NOVEL _RLIM/RNF12_ VARIANT DISRUPTS PROTEIN STABILITY AND FUNCTION TO

CAUSE SEVERE TONNE–KALSCHEUER SYNDROME Article Open access 05 May 2021 BIALLELIC _ATP2B1_ VARIANTS AS A LIKELY CAUSE OF A NOVEL NEURODEVELOPMENTAL MALFORMATION SYNDROME WITH PRIMARY

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utility and improves clinical management in paediatric medicine. NPJ Genom Med. 2016;1:15012. Article  CAS  PubMed  PubMed Central  Google Scholar  Download references 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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * School of

Biological Sciences, The University of Auckland, Auckland, New Zealand Jessie Poquérusse, Whitney Whitford, Russell G. Snell, Klaus Lehnert & Jessie C. Jacobsen * Centre for Brain

Research, The University of Auckland, Auckland, New Zealand Jessie Poquérusse, Whitney Whitford, Russell G. Snell, Klaus Lehnert & Jessie C. Jacobsen * Genetic Health Service New

Zealand, Auckland City Hospital, Auckland, New Zealand Juliet Taylor & Salam Alburaiky Authors * Jessie Poquérusse View author publications You can also search for this author inPubMed 

Google Scholar * Whitney Whitford View author publications You can also search for this author inPubMed Google Scholar * Juliet Taylor View author publications You can also search for this

author inPubMed Google Scholar * Salam Alburaiky View author publications You can also search for this author inPubMed Google Scholar * Russell G. Snell View author publications You can also

search for this author inPubMed Google Scholar * Klaus Lehnert View author publications You can also search for this author inPubMed Google Scholar * Jessie C. Jacobsen View author

publications You can also search for this author inPubMed Google Scholar 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. ETHICS DECLARATIONS 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). PATIENT CONSENT Consent was obtained from the patient’s family for publication of this

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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 Download citation * Received: 05 April 2021 * Revised: 05 June 2021 * Accepted: 20 June 2021 * Published: 09 July 2021 * Issue Date: January 2022 *

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