Ataxia and cerebellar anomalies - childhood onset

Gene: SART3

Green List (high evidence)

Comment on list classification: There are six unrelated families reported with biallelic SART3 variants and Intellectual disability, Neurodevelopmental defects and Developmental delay with 46,XY GONadal dysgenesis. Cerebellar vermis atrophy was reported in five of six families (although mild in three). Hence, this gene can be promoted to green rating in the next GMS update.

Created: 3 Nov 2026, 8:26 p.m. | Last Modified: 3 Nov 2026, 8:26 p.m.

Panel Version: 9.43

PMID:37296101 (2023) reported nine individuals from six different families presenting with a congenital syndrome characterised by gonadal dysgenesis in 46,XY individuals, intellectual disability, global developmental delay and overlapping neurological findings, including hypoplasia of the corpus callosum, cerebral and cerebellar anomalies. They were identified with either homozygous or compound heterozygous variants in the SART3 gene.

Severity of ID was severe in four patients, profound in one, moderate in one, mild-moderate in two and unreported in one. The age of patients at first examination ranged from 1 month to 7 years of age. Spasticity was reported in three patients (mild in two), mild ataxia reported in two and three patients were not walking on last examination. Cerebellar vermis atrophy was reported in six patients, of which it was mild in four.

Knockdown of the Drosophila orthologue of SART3 revealed a conserved role in testicular and neuronal development and human induced pluripotent stem cells carrying patient variants in SART3 demonstrated aberrant gonadal and neuronal differentiation in vitro. The authors tentatively termed this a spliceosomopathy as INDYGON syndrome (Intellectual disability, Neurodevelopmental defects and Developmental delay with 46,XY GONadal dysgenesis).

This gene has been associated with relevant phenotype in Gene2Phenotype (with 'moderate' rating on the DD panel), but not yet in OMIM (last accessed 03 November 2026).
Sources: Literature

Created: 3 Nov 2026, 8:15 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092; 46 XY differences of sex development, MONDO:0020040

Publications

• 37296101