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| Paediatric disorders - additional genes v1.96 | TSPYL1 | Arina Puzriakova Tag for-review was removed from gene: TSPYL1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v1.96 | TSPYL1 | Sarah Leigh commented on gene: TSPYL1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v1.95 | TSPYL1 |
Arina Puzriakova Source Expert Review Green was added to TSPYL1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Paediatric disorders - additional genes v1.73 | TSPYL1 | Eleanor Williams Classified gene: TSPYL1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v1.73 | TSPYL1 | Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber, but with a green recommendation for GMS review. 3 cases reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v1.73 | TSPYL1 | Eleanor Williams Gene: tspyl1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v1.72 | TSPYL1 | Eleanor Williams Tag for-review tag was added to gene: TSPYL1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Paediatric disorders - additional genes v1.72 | TSPYL1 |
Eleanor Williams changed review comment from: Associated with Sudden infant death with dysgenesis of the testes syndrome #608800 (AR) in OMIM. 3 independent cases with biallelic variants in TSPYL1 in patients with Sudden Infant Death with Dysgenesis of the Testes syndrome reported. 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. PMID: 15273283 - Puffenberger et al 2004 - report 21 individuals from a large Old Order Amish kinship with a phenotype of sudden infant death (from cardiac and respiratory arrest) with dysgenesis of the testes in males. A homozygous frameshift mutation c.457dupG (p.Glu153Glyfs*17) was detected after autozygosity scanning and sequencing of the the TSPYL (now known as TSPYL1) gene. All parents were heterozygous for the mutation. Functional experiments showed that there was a loss of nuclear localization of truncated TSPYL Two reports where SIDS cases were screened for TSPYL1 variants but only heterozygous variants were found: PMID: 25449952 - Schubert et al 2015 - screened TSPYL1 in 165 SIDS cases with mostly Swiss ethnic origin, and 163 German control adults. 8 known polymorphisms were detected, 3 affected individuals were found to have rare heterozygous missense variants (1 x c.106C>G (p.Leu36Val), 2 x c.1098C>A, p.Phe366Leu). The p.Phe366Leu variants was also found in a control individual. 2 silent rare variants were also found (1 case, 1 control). PMID: 16418600 - Hering et al 2006 - screen TSPYL1 in 126 SIDS cases and 261 controls. Found one female one female patient with a heterozygous p.F366L amino acid polymorphism which was not found in the controls. Concluded that the genetic analysis of TSPYL1 was of limited significance in the differential diagnosis of SIDS without dysgenesis of the testes. Reports where male infertility cases were screened for TSPYL1 variants: PMID: 19463995 - Vinci et al 2009 - screened 100 individuals with anomalies of testicular development or function for mutations in the TSPYL1 gene. 2 heterozygous variants reported. One in a 46,XY female with complete gonadal dysgenesis (p.K320R in the conserved NAP domain) and a 46,XY male with idiopathic azoospermia (p.R89H). PMID: 22137496 - Javaher et al 2012 - screen 104 infertile men for variants in TSPYL1. 2 potentially pathogenic heterozygous variants identified. 1 with azoospermia had a c.419C>G (p.Ser140Cys) variant and 1 with OAT syndrome had the rare c.1098C>A (p.Phe366Leu). However, 1 fertile man was also found to be heterozygous for the rare variant c.487G>A (p.Val163Ile). The authors concluded that TSPYL1 variants did not play a major role in idiopathic male infertility and would not recommend inclusion in diagnostic screening. Sources: Literature; to: Associated with Sudden infant death with dysgenesis of the testes syndrome #608800 (AR) in OMIM. 3 independent cases with biallelic variants in TSPYL1 in patients with Sudden Infant Death with Dysgenesis of the Testes syndrome reported. 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. PMID: 15273283 - Puffenberger et al 2004 - report 21 individuals from a large Old Order Amish kinship with a phenotype of sudden infant death (from cardiac and respiratory arrest) with dysgenesis of the testes in males. A homozygous frameshift mutation c.457dupG (p.Glu153Glyfs*17) was detected after autozygosity scanning and sequencing of the the TSPYL (now known as TSPYL1) gene. All parents were heterozygous for the mutation. Functional experiments showed that there was a loss of nuclear localization of truncated TSPYL Two reports where SIDS cases were screened for TSPYL1 variants but only heterozygous variants were found: PMID: 25449952 - Schubert et al 2015 - screened TSPYL1 in 165 SIDS cases with mostly Swiss ethnic origin, and 163 German control adults. 8 known polymorphisms were detected, 3 affected individuals were found to have rare heterozygous missense variants (1 x c.106C>G (p.Leu36Val), 2 x c.1098C>A, p.Phe366Leu). The p.Phe366Leu variants was also found in a control individual. 2 silent rare variants were also found (1 case, 1 control). PMID: 16418600 - Hering et al 2006 - screen TSPYL1 in 126 SIDS cases and 261 controls. Found one female one female patient with a heterozygous p.F366L amino acid polymorphism which was not found in the controls. Concluded that the genetic analysis of TSPYL1 was of limited significance in the differential diagnosis of SIDS without dysgenesis of the testes. |
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| Paediatric disorders - additional genes v1.72 | TSPYL1 |
Eleanor Williams gene: TSPYL1 was added gene: TSPYL1 was added to Paediatric disorders - additional genes. Sources: Literature Mode of inheritance for gene: TSPYL1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TSPYL1 were set to Sudden infant death with dysgenesis of the testes syndrome OMIM:608800; sudden infant death-dysgenesis of the testes syndrome MONDO:0012124 Review for gene: TSPYL1 was set to GREEN Added comment: Associated with Sudden infant death with dysgenesis of the testes syndrome #608800 (AR) in OMIM. 3 independent cases with biallelic variants in TSPYL1 in patients with Sudden Infant Death with Dysgenesis of the Testes syndrome reported. 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. PMID: 15273283 - Puffenberger et al 2004 - report 21 individuals from a large Old Order Amish kinship with a phenotype of sudden infant death (from cardiac and respiratory arrest) with dysgenesis of the testes in males. A homozygous frameshift mutation c.457dupG (p.Glu153Glyfs*17) was detected after autozygosity scanning and sequencing of the the TSPYL (now known as TSPYL1) gene. All parents were heterozygous for the mutation. Functional experiments showed that there was a loss of nuclear localization of truncated TSPYL Two reports where SIDS cases were screened for TSPYL1 variants but only heterozygous variants were found: PMID: 25449952 - Schubert et al 2015 - screened TSPYL1 in 165 SIDS cases with mostly Swiss ethnic origin, and 163 German control adults. 8 known polymorphisms were detected, 3 affected individuals were found to have rare heterozygous missense variants (1 x c.106C>G (p.Leu36Val), 2 x c.1098C>A, p.Phe366Leu). The p.Phe366Leu variants was also found in a control individual. 2 silent rare variants were also found (1 case, 1 control). PMID: 16418600 - Hering et al 2006 - screen TSPYL1 in 126 SIDS cases and 261 controls. Found one female one female patient with a heterozygous p.F366L amino acid polymorphism which was not found in the controls. Concluded that the genetic analysis of TSPYL1 was of limited significance in the differential diagnosis of SIDS without dysgenesis of the testes. Reports where male infertility cases were screened for TSPYL1 variants: PMID: 19463995 - Vinci et al 2009 - screened 100 individuals with anomalies of testicular development or function for mutations in the TSPYL1 gene. 2 heterozygous variants reported. One in a 46,XY female with complete gonadal dysgenesis (p.K320R in the conserved NAP domain) and a 46,XY male with idiopathic azoospermia (p.R89H). PMID: 22137496 - Javaher et al 2012 - screen 104 infertile men for variants in TSPYL1. 2 potentially pathogenic heterozygous variants identified. 1 with azoospermia had a c.419C>G (p.Ser140Cys) variant and 1 with OAT syndrome had the rare c.1098C>A (p.Phe366Leu). However, 1 fertile man was also found to be heterozygous for the rare variant c.487G>A (p.Val163Ile). The authors concluded that TSPYL1 variants did not play a major role in idiopathic male infertility and would not recommend inclusion in diagnostic screening. Sources: Literature |
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