Your new experience awaits. Try the new design now and help us make it even better

ORIGINAL RESEARCH article

Front. Genet.

Sec. Genetics of Common and Rare Diseases

Volume 16 - 2025 | doi: 10.3389/fgene.2025.1664424

Biallelic variants in the UTRN gene cause a novel form of multiple congenital arthrogryposis

Provisionally accepted
Evgeniya  MelnikEvgeniya Melnik1*Daria  AkimovaDaria Akimova1Tatiana  MarkovaTatiana Markova1Eugene  TatarskiyEugene Tatarskiy1Anna  TvorogovaAnna Tvorogova2Viktoria  ZabnenkovaViktoria Zabnenkova1Vladimir  KenisVladimir Kenis3Olga  AgranovichOlga Agranovich3Mikhail  SkoblovMikhail Skoblov1Elena  DadaliElena Dadali1
  • 1Research Centre for Medical Genetics, Moscow, Russia
  • 2Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia
  • 3H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery of the Ministry of Health of the Russian Federation, Saint Petersburg, Russia

The final, formatted version of the article will be published soon.

Arthrogryposis multiplex congenita (AMC) is a large group of congenital conditions characterized by joint contractures affecting two or more body areas. A part of AMC type is caused by heterozygous pathogenic variants in genes encoding sarcomeric components of skeletal muscle fibers. Here we report a 7-year-old boy with a phenotype including AMC with dysmorphic facial features, short stature, congenital malformations of brain, colon and lacrimal canal. Trio whole-genome sequencing identified compound heterozygosity in the UTRN gene, consisting of a splicing variant in intron 57 (c.8434+1G>A) and a large heterozygous deletion spanning exons 3–51 (NM_007124.3). It is known that utrophin, the product of the UTRN gene, is an autosomal homologue and a fetal form of a protein of skeletal muscles - dystrophin. The presence of multiple malformations in the patient's phenotype is consistent with ubiquitous expression of utrophin in the embryonic period. The RNA-seq analysis revealed that the splicing variant introduces a premature termination codon, which is predicted to result in a truncated protein shorter by 615 amino acids (p.Val2786Argfs*34), and the deletion leads to transcription of a shortened RNA isoform. We suggest that these variants are hypomorphic and partially retain protein function, which explains the clinical picture in the patient. In aggregate, our findings provide evidence that rare biallelic recessive variants in UTRN cause a novel autosomal recessive multiple congenital arthrogryposis.

Keywords: UTRN 1, utrophin 2, arthrogryposis multiplex congenita3, AMC4, novel phenotype5

Received: 11 Jul 2025; Accepted: 07 Oct 2025.

Copyright: © 2025 Melnik, Akimova, Markova, Tatarskiy, Tvorogova, Zabnenkova, Kenis, Agranovich, Skoblov and Dadali. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Evgeniya Melnik, evmel88@gmail.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.