Fig. 1: Bi-allelic variants in SART3 are associated with a syndrome characterised by developmental delay, intellectual disability and 46,XY-specific gonadal dysgenesis.

a The pedigrees of six families with affected children carrying bi-allelic SART3 variants. Arrows = probands. Both genetic sex (XX or XY) and gender (circle = female, square = male) are indicated. Families ISR1, ISR2 and TUN1 have homozygous variants. Families ISR3, ITA1, FRA1 have compound heterozygous variants. b–g Gonad histology in ISR2.2. b The left testis, resected at 9 months, was fibrotic. Both epididymis (box) and fallopian tube (arrow) were present. c Enlarged views of the left epididymis (insert from b) and d fallopian tube (arrow). e Histology of the right testis, resected at age 5, demonstrated widespread fibrosis and the presence of epididymis (dotted line) and fallopian tube (arrow). f Higher magnification of the epididymis, and g the fallopian tube. h–v MRI imaging. T1-weighted midline sagittal images demonstrating thin corpus callosum in j ISR1.2, l ISR2.1, n ISR2.2, p ITA1.1 and FRA1.1 (s and u, inversion recovery image 0.9 mm thick), and h absent corpus callosum in ISR1.1. Atrophy of the cerebellar vermis is observed in h ISR1.1, l ISR2.1, n ISR2.2 and in p ITA1.1. s, u In FRA1.1, sagittal imaging also revealed vermis atrophy, enlargement of the 4th ventricle, cisterna magna and hypoplastic pons. T2-weighted axial images at the level of the lateral ventricles demonstrated delayed myelination and atrophy of the white matter and ragged configuration of the posterior horn of the lateral ventricle in k ISR1.2, m ISR2.1 and o ISR2.2. r Coronal section for ITA1.1 shows cerebellar atrophy with q axial inversion recovery image showing mild ventriculomegaly. i ISR1.1 has colpocephaly with decreased white matter volume. t Axial T2-weighted image in FRA1.1 demonstrates ventriculomegaly with square-shaped frontal horns. v Atrophy of the cerebellar hemispheres is also observed in a coronal inversion recovery image. A anterior.