TECR – Intellectual Disability

This summary integrates evidence from multiple independent studies indicating a strong association between TECR (HGNC:4551) and intellectual disability (MONDO_0001071). In one study of chromosomal rearrangements, a 1.2 Mb deletion (19p13.12-p13.13) encompassing TECR was linked to a mild intellectual disability phenotype, thereby highlighting the potential relevance of this gene in cognitive processes (PMID:22419660).

A second case report detailed an individual of Hutterite ancestry with autosomal recessive intellectual disability in whom a homozygous missense variant was identified. This variant, reported as c.545C>T (p.Pro182Leu), was originally observed in an affected sibship and subsequently extended by the description of a sporadic case, strengthening the evidence for TECR-related pathology (PMID:35709344).

The genetic evidence supports an autosomal recessive inheritance mode for TECR-related intellectual disability. Segregation analysis in the reported families indicates that affected siblings harbor the same homozygous variant, reinforcing the pathogenicity of the mutation (PMID:35709344).

Complementary functional studies have provided critical insights into the pathogenic mechanism. One study demonstrated that the c.545C>T (p.Pro182Leu) mutation leads to reduced trans-2-enoyl-CoA reductase activity and protein instability, thereby impairing very long-chain fatty acid synthesis and altering sphingolipid profiles (PMID:24220030). A subsequent investigation further elucidated the catalytic mechanism of TECR, where alterations in key residues resulted in markedly diminished enzyme function (PMID:38224948).

The convergence of genetic and experimental data yields a coherent narrative that TECR plays a critical role in neurodevelopment. The identification of a recurrent homozygous variant in unrelated individuals, coupled with functional validation demonstrating impaired enzymatic activity, establishes a robust association with intellectual disability.

Key take‑home sentence: Incorporating TECR into diagnostic testing panels for intellectual disability can enhance molecular diagnosis, particularly in populations with founder mutations.

References

• American journal of medical genetics. Part A • 2012 • Expanding the spectrum of rearrangements involving chromosome 19: a mild phenotype associated with a 19p13.12-p13.13 deletion PMID:22419660
• South Dakota medicine : the journal of the South Dakota State Medical Association • 2022 • Individual with Homozygous TECR Variant Expands Upon the Existing Phenotype for a Hutterite Founder Mutation PMID:35709344
• The Journal of biological chemistry • 2013 • Mutation for nonsyndromic mental retardation in the trans-2-enoyl-CoA reductase TER gene involved in fatty acid elongation impairs the enzyme activity and stability, leading to change in sphingolipid profile PMID:24220030
• The Journal of biological chemistry • 2024 • Catalytic mechanism of trans-2-enoyl-CoA reductases in the fatty acid elongation cycle and its cooperative action with fatty acid elongases PMID:38224948

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