QRICH1 was first reported in relation to autosomal dominant syndromic complex neurodevelopmental disorder in 2018 (Ververi et al., PMID: 28692176). QRICH1 encodes a protein that functions as a mediator in the integrated stress response by controlling transcription of protein homeostasis under endoplasmic reticulum stress. Clinical features in affected individuals include developmental delay, intellectual disability, mild dysmorphic facial features, hypotonia, short stature, autism spectrum disorder, and seizures (PMID: 34859529). Additional, more variable features may include scoliosis, cardiac, renal and structural brain abnormalities.
Seven variants (nonsense, frameshift, and missense) reported in 7 probands in 3 publications (PMIDs: 28692176, 30281152, 33009816) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. The mechanism of pathogenicity is loss of function. This gene-disease relationship is also supported by experimental evidence, including a mouse model (PMID: 30281152).
In summary, there is definitive evidence supporting the relationship between QRICH1 and autosomal dominant syndromic complex neurodevelopmental disorder. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on June 15, 2022 (SOP version 9).
QRICH1 variants were first reported in relation to autosomal dominant syndromic complex neurodevelopmental disorder in 2018 (PMID: 28692176). QRICH1 encodes a protein that functions as a mediator in the integrated stress response by controlling transcription of protein homeostasis under endoplasmic reticulum stress. Clinical features in affected individuals include developmental delay, intellectual disability, mild dysmorphic facial features, hypotonia, short stature, autism spectrum disorder, and seizures (PMID: 34859529). Additional, more variable features may include scoliosis, cardiac, renal and structural brain abnormalities.
At least 7 unique variants (nonsense, frameshift, and missense) reported in 7 probands in 3 publications (PMIDs: 28692176, 30281152, 33009816) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. The mechanism of pathogenicity is loss of function. This gene-disease relationship is also supported by experimental evidence, including a mouse model (PMID: 30281152).
In summary, there is definitive evidence supporting the relationship between QRICH1 and autosomal dominant syndromic complex neurodevelopmental disorder. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on June 15, 2022 (SOP version 9).
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