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This summary describes the association between NIT1 and EAST syndrome, a recessively inherited condition characterized by intellectual disability (PMID:31640787). Multiple studies using whole‑exome sequencing have consistently identified homozygous variants in NIT1 among affected individuals, thereby establishing a strong genetic link to the clinical phenotype.
In one multi‑patient study, a family with four affected individuals showed clear segregation of rare homozygous variants, including the reported variant c.727C>T (p.Arg243Trp) (PMID:31640787). The identification of this variant in independent probands strengthens the genetic evidence for a causative role of NIT1 in EAST syndrome.
Genetic evidence is further reinforced by the detection of a full‐coding change in NIT1 that meets ClinGen criteria. In the available reports, the variant spectrum includes complete coding changes, with c.727C>T (p.Arg243Trp) being representative of the loss‑of‑function mechanism expected from homozygous mutations, which are consistent with an autosomal recessive inheritance pattern.
Although functional assays directly evaluating NIT1 in EAST syndrome are limited, the overall experimental data from related genes and the consistent segregation pattern support the hypothesized loss‑of‑function mechanism. This includes predictive in silico analyses and the observed absence of NIT1 protein in related contexts, lending further support to its role in the pathogenesis of the disorder (PMID:31640787).
No significant conflicting evidence has been reported; however, additional functional studies specific to NIT1 in EAST syndrome would further elucidate its pathogenic mechanism. The integration of genetic findings with existing experimental data provides a coherent narrative that supports the involvement of NIT1 in the clinical presentation of intellectual disability in EAST syndrome.
Key take‑home sentence: The strong genetic evidence combined with supportive, albeit limited, functional data endorses the use of NIT1 variant screening in diagnostic decision‑making for EAST syndrome.
Gene–Disease AssociationStrongFour affected patients with demonstrable segregation and identification across multi‑patient studies provide robust support for the association of NIT1 with EAST syndrome (PMID:31640787). Genetic EvidenceStrongThe detection of the homozygous variant c.727C>T (p.Arg243Trp) in multiple unrelated probands along with confirmed segregation in affected individuals fulfills ClinGen genetic criteria. Functional EvidenceLimitedWhile supportive loss‑of‑function predictions and protein absence data from related assessments exist, gene‑specific functional assays for NIT1 in EAST syndrome are currently lacking, necessitating further investigation (PMID:31640787). |