PUS3 Syndrome
OVERVIEW
What Is PUS3 Syndrome?
Gene Function
The PUS3 gene provides instructions for making the pseudouridylate synthase 3 (PUS3) enzyme.
Role in the Body
This enzyme is crucial for modifying tRNA (transfer RNA) — a molecule essential for protein production.
Impact of Mutations
The negative consequences on overall health and life can range from serious to devastating, with a tendency to worsen over time and lead to lifelong disability.
Intellectual disability
Microcephaly
Epilepsy
Growth failure
Heart defects
Kidney issues
Clinical Symptoms
SYMPTOMS
Common Symptoms & Clinical Features
Core Neurological Symptoms
Intellectual disability (moderate to severe)
Global developmental delay
Delayed psychomotor development
Epileptic seizures
Behavioral issues and abnormalities
Physical Features
Microcephaly (small head circumference)
Growth delay/short stature
Hypotonia (low muscle tone/muscle weakness)
Facial features (mild to distinctive facial dysmorphism)
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Other Features
Visual impairments (nystagmus, optic disc pallor, astigmatism, retinal dystrophy)
Cardiac abnormalities
Mitochondrial dysfunction causing muscle weakness and fatigue
Leukoencephalopathy and nephropathy
Cerebellar hypoplasia, scoliosis, feeding difficulties, sensory integration disorder
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The Most Reliable Test
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The Whole Exome Sequencing (WES) test is the gold standard for confirming a PUS3 gene mutation.
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It provides a comprehensive analysis of all protein-coding regions in the genome.
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The test is performed for the child and both parents simultaneously for higher accuracy.
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The Value of Genetic Confirmation
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WES offers definitive confirmation of PUS3 syndrome
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It helps guide appropriate care and improve quality of life
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It connects families to research and support — every confirmed case matters
ARTICLES
Scientific Articles & Publications About PUS3
Destabilization of mutated human PUS3 protein causes intellectual disability.
Lin TY, Smigiel R, Kuzniewska B, Chmielewska JJ, Kosińska J, Bela M, et al.
Hum Mutat. 2022 Dec;43(12):2063–2078.
DOI: 10.1002/humu.24471.
PMID: 36125428; PMCID: PMC10092196.
A homozygous truncating mutation in PUS3 expands the role of tRNA modification in cognition.
Shaheen R, Han L, Faqeih E, Ewida N, Alobeid E, Phizicky EM, Alkuraya FS.
Hum Genet. 2016 Jul;135(7):707–713.
DOI: 10.1007/s00439-016-1665-7.
PMID: 27055666; PMCID: PMC5152754.