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ORIGINAL RESEARCH article

Front. Pediatr.

Sec. Genetics of Common and Rare Diseases

Volume 13 - 2025 | doi: 10.3389/fped.2025.1699544

A novel frameshift variant in the MED13 gene causing intellectual developmental disorder-61 in a Chinese family

Provisionally accepted
Qi  YangQi Yang*Qiang  ZhangQiang ZhangSheng  YiSheng YiGaojie  HuangGaojie HuangXunzhao  ZhouXunzhao ZhouShang  YiShang YiJingsi  LuoJingsi Luo*
  • Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Other, Nanning, China

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

Intellectual developmental disorder type 61 (MRD61) is an extremely rare autosomal dominant disorder caused by variants in the MED13 gene. This gene encodes a subunit of the mediator complex, which is also known as TRAP, SMCC, DRIP or ARC. This complex functions as a transcriptional coactivator and is essential for the expression of almost all genes. To date, only 26 cases of MRD61 have been reported worldwide. The main symptoms are intellectual disability (ID) of varying degrees, developmental delay (DD), hypotonia during infancy, facial dysmorphism, language impairment, restricted growth, skeletal and limb abnormalities, and behavioral abnormalities. In this study, we recruited a Chinese family in which two individuals were diagnosed with MRD61. Whole-exome sequencing of the proband revealed a novel heterozygous frameshift variant in the MED13 gene (NM_005121.3): c.5641delinsTC (p.R1882Sfs*9). This variant was inherited from the affected mother and was subsequently confirmed in both the proband and her other family members using Sanger sequencing. The dysmorphology profile of both patients described here is similar to that associated with MRD61. Compared with previously reported cases of MRD61, the proband presented with congenital megacolon, a previously unreported complication. Additionally, skeletal and limb deformities, eye or vision abnormalities, behavioral issues and brain abnormalities were absent in our patients. This is the first report of MED13-associated intellectual developmental disorder-61 in China. This molecular diagnosis expands the known genetic spectrum of MRD61. Furthermore, the specific manifestations observed in these patients with this condition provide valuable additional clinical insight into the syndrome.

Keywords: Intellectual developmental disorder type 61, MED13 gene, Novel variant, Whole-exome sequencing, Unreported complication

Received: 05 Sep 2025; Accepted: 06 Oct 2025.

Copyright: © 2025 Yang, Zhang, Yi, Huang, Zhou, Yi and Luo. 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:
Qi Yang, 15625056073@163.com
Jingsi Luo, yangqisklmg126@126.com

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