Disease relevance of TSPYL1

• Mapping of sudden infant death with dysgenesis of the testes syndrome (SIDDT) by a SNP genome scan and identification of TSPYL loss of function [1].
• Furthermore, we show that other members of the TSPYL gene family are epigenetically silenced in gliomas and dissect the contribution of individual DNA methyltransferases to the aberrant promoter hypermethylation events [2].
• Because SIDDT is the result of homozygous TSPYL1 mutations, this heterozygous exchange cannot solely explain the sudden death in this child [3].

High impact information on TSPYL1

• This interval contained 27 genes, including two testis-specific Y-like genes (TSPYL and TSPYL4) of unknown function [1].
• Sequence analysis of the TSPYL gene in affected individuals identified a homozygous frameshift mutation (457_458insG) at codon 153, resulting in truncation of translation at codon 169 [1].
• Specific recruitment of ZFP106 via amino acids 412-781 into TSPYL-positive nucleoplasmic bodies requires a TSPYL domain absent in the mutant protein of patients with testis dysgenesis [4].
• DENTT contains a conserved 191-residue domain that shows significant identity to, and defines, the TSPY/TSPY-like/SET/NAP-1 superfamily [5].
• PURPOSE: The study's purpose was to reveal a possible role of TSPYL1 in SIDS [3].

Biological context of TSPYL1

• A human TSPYL gene was localized on chromosome 6 and a murine Tspyl gene was localized on chromosome 10 [6].
• Both the human and murine Tspyl homologs lack introns over the entire region so far investigated and are thought to have arisen by an ancient retroposition event [6].
• Retroposition of Tspyl genes is supported by the isolation of a murine Tspyl pseudogene on chromosome 12 which also lacks intronic sequences, and by its observed proximity to an R element, a family of dispersed repetitive DNA [6].
• BACKGROUND: Sudden infant death syndrome (SIDS) constitutes the most frequent cause of death in the postperinatal period in Germany. Recently, a lethal phenotype characterized by sudden infant death with dysgenesis of the testes syndrome (SIDDT) was identified to be caused by loss of function mutations in the TSPYL1 gene [3].

Analytical, diagnostic and therapeutic context of TSPYL1

• Genetic analysis of TSPYL1 seems to be of limited significance in the differential diagnosis of SIDS without dysgenesis of the testes [3].

References