Genetic Epilepsy

Gene: TSPYL1

Green List (high evidence)

Further evidence of seizure phenotype

Created: 4 Jan 2024, 1:51 a.m. | Last Modified: 4 Jan 2024, 1:51 a.m.

Panel Version: 0.2138

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sudden infant death with dysgenesis of the testes syndrome MIM#608800

Publications

• PMID: 36082874

Green List (high evidence)

First identified in a large Amish family - lethal disease characterized by sudden infant death from cardiorespiratory arrest with dysgenesis of the testes (Puffenberger et al 2004). Cases in non-Amish families reported with additional phenotypic features noted including epilepsy (Slater et al 2020 and Buyse et al 2020)
Sources: Expert list, Literature

Created: 7 Oct 2021, 11:50 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sudden infant death with dysgenesis of the testes syndrome - 608800; sudden infant death-dysgenesis of the testes syndrome MONDO:0012124

Publications

• 32885560
• 15273283
• 33075815

Green List (high evidence)

2 new cases of Sudden infant death with dysgenesis of the testes syndrome reported, both with the same frameshift variant:

PMID: 32885560 - Slater et al 2020 - report a Hispanic, phenotypically female infant with poor feeding and abnormal motor movements noted at birth. Mild T-cell lymphopenia, absent uterus and adnexal structures, with no gonads visible and intractable epilepsy are also reported. The patient died of respiratory failure at 8 months of age. Exome sequencing revealed homozygosity for a frameshift variant in TSPYL1 (c.725_726delTG, p.Val242GlufsTer52). The variant has a frequency of 0.002% in gnomAD but has not been reported in the homozygous state.

PMID: 33075815 - Buyse et al 2020 - report 3 affected siblings from a consanguineous Turkish family. The phenotype was characterized by visceroautonomic dysfunction, severe postnatal progressive neurological abnormalities, visual impairment, testicular dysgenesis in males and sudden death at infant age. WES analysis found a homozygous frameshift variant p.Val242GlufsTer52 in TSPYL1 in the affected siblings. The variant is found in gnomAD at a MAF of 0.0021%, but no homozygous individuals are reported. The parents and one unaffected sibling were heterozygous for the variant. The truncated protein was retained in the Golgi in patient fibroblasts whereas in control fibroblasts the full length protein was found in the nucleus. Patient cells also showed prolonged S and G2 phases with reduced cellular proliferation rates. Tspyl1 depleted zebrafish showed a similar phenotype with early lethality, defects in neurogenesis and cardiac dilation.

Created: 9 Jan 2021, 11 a.m. | Last Modified: 9 Jan 2021, 11 a.m.

Panel Version: 0.6026

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sudden infant death with dysgenesis of the testes syndrome OMIM:608800; sudden infant death-dysgenesis of the testes syndrome MONDO:0012124

Publications

• 32885560
• 33075815

I don't know

Limited evidence supporting gene disease association. Single homozygous variant reported in an Amish Community with sudden infant death with dysgenesis of the testes in males. Amber/Red. PMID: 15273283: Homozygous frameshift variant (not present in gnomad) identified in a large Old Order Amish community with sudden infant death (from cardiac and respiratory arrest) with dysgenesis of the testes in males. PMID: 19463995: 2 heterozygous variants reported in a 46,XY female with complete gonadal dysgenesis and a 46,XY male with idiopathic azoospermia. Both variants present in gnomad 5 hets each and no homozygotes. PMID: 22137496: 2 variants reported with male idiopathic infertility. S140C present in gnomad (8 hets, 0 hom), F366L present (957 hets, 3 homs). Authors concluded that TSPYL1 would not be recommended as part of routine diagnosis screenning. PMID: 25449952; 16418600: Concluded as not causative of the associated phenotype and has limited evidence for screening.

Created: 15 Jul 2020, 8:42 a.m. | Last Modified: 15 Jul 2020, 8:42 a.m.

Panel Version: 0.3359

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sudden infant death with dysgenesis of the testes syndrome (MIM#608800)

Publications

• 15273283
• 19463995
• 22137496
• 25449952
• 16418600