Unraveling a Diagnostic Enigma: A <scp> <i>TECPR2</i> </scp> Case Solved Through Multi‐Omic Genomics
TECPR2 is a key regulator of autophagy, encoded by the TECPR2 gene. Pathogenic variants in this gene have been linked to a rare hereditary sensory and autonomic neuropathy with intellectual disability (HSAN9). We report a teenage female with a syndromic intellectual disability disorder associated with neuromuscular abnormalities. Multi-omics analysis including genomics, transcriptomics, and proteomics, together with muscle biopsy from the affected individual, were used in this clinical case. Through trio exome sequencing we identified two heterozygous variants in the TECPR2 gene, NM_014844.4: c.480G>A; p.(Gln160=) and c.2846C>A; p.(Ala949Glu). Both were classified as variants of uncertain significance due to the lack of supporting evidence for pathogenicity. Subsequent long-read sequencing phased the variants and confirmed they were in trans. Additional functional studies using RNAseq and proteomics analyses verified the pathogenicity of the variants. This case study demonstrated the value of a multi-omics assisted analysis, which complemented the traditional phenotype-first approach in reaching a definitive clinical diagnosis.
Authors
- Teresa Zhao (ORCID: https://orcid.org/0000-0002-3445-3898)
- David R. Thorburn (ORCID: https://orcid.org/0000-0002-7725-9470)
- Meagan J. McGrath (ORCID: https://orcid.org/0000-0002-9414-6558)
- Katrina M. Bell (ORCID: https://orcid.org/0000-0001-6109-3667)
- Tanavi Sharma (ORCID: https://orcid.org/0000-0002-6054-315X)
- Monique Dunstan (ORCID: https://orcid.org/0009-0004-0255-8312)
- David A. Stroud
- Sebastian Lunke (ORCID: https://orcid.org/0000-0002-7168-0723)
- Undiagnosed Diseases Network (UDN‐Aus)
- Andrew P. Fennell (ORCID: https://orcid.org/0000-0001-6744-1810)
- John Christodoulou (ORCID: https://orcid.org/0000-0002-8431-0641)
- Catriona McLean (ORCID: https://orcid.org/0000-0002-0302-5727)
Institutions
- The University of Sydney (AU)
- Royal Children's Hospital (AU)
- The University of Melbourne (AU)
- Discovery Institute (US)
- Monash Alfred Psychiatry Research centre (AU)
- Victorian Clinical Genetics Services (AU)
- Monash Health (AU)
- Murdoch Children's Research Institute (AU)
- Alfred Health (AU)
- Monash University (AU)
Publication Details
- Journal
- American Journal of Medical Genetics Part A
- Published
- 2026-05-11
- DOI
- https://doi.org/10.1002/ajmg.a.70191
- Primary Topic
- Hereditary Neurological Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Murdoch Children's Research Institute
- University of Melbourne
- Garvan Institute of Medical Research
- Australian Genomics Health Alliance
- Mito Foundation
- National Health and Medical Research Council
- Medical Research Future Fund