Severe microcephaly

Gene: SPOUT1

Green List (high evidence)

Comment on publications: PMID: 39962046 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

Created: 17 Mar 2025, 1:47 p.m. | Last Modified: 17 Mar 2025, 1:47 p.m.

Panel Version: 7.62

PMID: 39962046 reports the association of biallelic SPOUT1 variants with SPOUT1 Associated Development delay Microcephaly Seizures Short stature. In this study, a total of 18 SPOUT1 variants were found in 28 individuals from 21 unrelated families. Intellectual disability was evident in 10/10 families where it could be ascertained, seizures were reported in 16/21 of the families, short stature was seen in 13/15 families where it could be measured and microcephaly was evident in 18/21 cases, with clearly severe microcephaly in 5 cases (PMID: 39962046, supplementary table 1).
SPOUT1 variant zebra fish models showed reduction in larval head size with concomitant apoptosis and the human SPOUT1 missense variants were pathogenic in complementation assays in zebrafish (PMID: 39962046).
Sources: Literature

Created: 17 Mar 2025, 1:44 p.m. | Last Modified: 31 Mar 2025, 11:20 a.m.

Panel Version: 7.23

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
SPOUT1 Associated Development delay Microcephaly Seizures Short stature

Publications

• 39962046