Open Access

RMRP variants inhibit the cell cycle checkpoints pathway in cartilage‑hair hypoplasia

  • Authors:
    • Jian Gao
    • Junge Zheng
    • Shiguo Chen
    • Sheng Lin
    • Shan Duan
  • View Affiliations

  • Published online on: January 27, 2025     https://doi.org/10.3892/mmr.2025.13446
  • Article Number: 81
  • Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cartilage‑hair hypoplasia (CHH) is an autosomal recessive form of metaphyseal chondrodysplasia caused by RNA component of mitochondrial RNA processing endoribonuclease (RMRP) gene variants; however, its molecular etiology remains unclear. Whole‑exome sequencing was performed to detect possible pathogenic variants in a patient with a typical short stature and sparse hair. A co‑segregation analysis was also conducted and variants in the family members of the patient were confirmed by Sanger sequencing. A novel compound heterozygous variant in RMRP (NR_003051.4: n.‑21_‑2dup and n.197C>T) was identified in the affected patient. Data from 2 years and 4 months of follow‑up showed a positive effect of growth hormone (GH) therapy on height. Subsequently, two gene expression profiles associated with CHH were obtained from the EMBL‑EBI ENA and ArrayExpress databases. Differentially expressed genes between patients with CHH and healthy controls were selected using R software and were subjected to core analysis using ingenuity pathway analysis (IPA) software. IPA core analysis showed that the ‘cell cycle checkpoints’ was the most prominent canonical pathway, and the top enriched diseases and functions included various types of cancer, immunological diseases, development disorders and respiratory diseases. The integrative analysis displayed that RMRP can regulate the aberrant expression of downstream targets mainly via the transcription factor TP53, which results in the inhibition of ‘cell cycle checkpoints’; eventually, functions associated with the CHH phenotype, such as ‘growth failure or short stature’ are activated. In conclusion, novel disease‑causing genetic variants of RMRP expand the genetic etiology of CHH, which must be clinically differentiated from achondroplasia. The findings of the present study provide new insights into the mechanisms underlying CHH.
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March-2025
Volume 31 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Gao J, Zheng J, Chen S, Lin S and Duan S: RMRP variants inhibit the cell cycle checkpoints pathway in cartilage‑hair hypoplasia. Mol Med Rep 31: 81, 2025.
APA
Gao, J., Zheng, J., Chen, S., Lin, S., & Duan, S. (2025). RMRP variants inhibit the cell cycle checkpoints pathway in cartilage‑hair hypoplasia. Molecular Medicine Reports, 31, 81. https://doi.org/10.3892/mmr.2025.13446
MLA
Gao, J., Zheng, J., Chen, S., Lin, S., Duan, S."RMRP variants inhibit the cell cycle checkpoints pathway in cartilage‑hair hypoplasia". Molecular Medicine Reports 31.3 (2025): 81.
Chicago
Gao, J., Zheng, J., Chen, S., Lin, S., Duan, S."RMRP variants inhibit the cell cycle checkpoints pathway in cartilage‑hair hypoplasia". Molecular Medicine Reports 31, no. 3 (2025): 81. https://doi.org/10.3892/mmr.2025.13446