title: Variants in TSPYL1 are not associated with sudden infant death syndrome in a cohort of deceased infants from Switzerland.
abstract: Sudden infant death syndrome (SIDS) is currently the major cause of an unexpected and unexplained death of infants in the first year of lifetime in industrialized countries. Besides environmental factors also genetic factors have been identified as risk factors for SIDS. Notably, the mutation c.457dupG (p.Glu153Glyfs*17) in the TSPYL1 gene has been reported to cause autosomal recessive sudden infant death with dysgenesis of the testes syndrome (SIDDT) in an Old Order Amish community in Pennsylvania. The purpose of this study was to analyze whether variants of TSPYL1 are associated with the sudden infant death syndrome (SIDS) in the area of Europe from which the Amish descended. Mutation analysis of the entire TSPYL1 gene was performed in a cohort of 165 SIDS cases with mostly Swiss ethnic origin, in comparison to 163 German controls. Eight known polymorphisms were detected, none of which was significantly associated with SIDS. One deceased girl was heterozygous for the hitherto unreported TSPYL1 variant c.106C>G (p.Leu36Val), and two affected girls were heterozygous for the rare known TSPYL1 variant rs140756663 (c.1098C>A, p.Phe366Leu). In addition, one deceased boy was heterozygous for the rare common silent nucleotide substitution c.718C>T (p.Leu240Leu, rs150144081), while one control was heterozygous for the rare silent nucleotide substitution rs56190632 (c.760C>T; p.Leu254Leu). In silico analyses predicted a likely non-pathogenic effect for p.Leu36Val and p.Phe366Leu, respectively, although protein features might be affected. The Amish founder mutation was not detected in the analyzed SIDS cases and controls. Mutations and polymorphisms in the TSPYL1 gene were not associated with SIDS in a cohort of 165 deceased Swiss infants.
authors.affiliation: Institute for Human Genetics, Hannover Medical School, Carl-Neuberg Str.1, D-30625 Hannover, Germany. Electronic address: schubert.steffi@mh-hannover.de.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schubert
authors.affiliation: Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, CH-8057 Zurich, Switzerland.
authors.forename: Cordula
authors.initials: C
authors.lastname: Haas
authors.affiliation: Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, CH-8057 Zurich, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Bartsch
authors.affiliation: Institute for Human Genetics, Hannover Medical School, Carl-Neuberg Str.1, D-30625 Hannover, Germany.
authors.forename: Mandana
authors.initials: M
authors.lastname: Mirshekarnejad
authors.affiliation: Institute for Human Genetics, Hannover Medical School, Carl-Neuberg Str.1, D-30625 Hannover, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kohrs
authors.affiliation: Institute for Human Genetics, Hannover Medical School, Carl-Neuberg Str.1, D-30625 Hannover, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Roettinger
authors.affiliation: Institute of Biostatistics, Hannover Medical School, Carl-Neuberg Str.1, D-30625 Hannover, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Grosshennig
authors.affiliation: Institute for Human Genetics, Hannover Medical School, Carl-Neuberg Str.1, D-30625 Hannover, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Stuhrmann
authors.affiliation: Institute for Human Genetics, Hannover Medical School, Carl-Neuberg Str.1, D-30625 Hannover, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Scholz
authors.affiliation: Institute for Human Genetics, Hannover Medical School, Carl-Neuberg Str.1, D-30625 Hannover, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Schmidtke
mesh_terms: D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D005858:Germany; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013398:Sudden Infant Death / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D013557:Switzerland; D044465:White People / Q000208:ethnology* / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; C510183:TSPYL1 protein, human
keywords: Genetic risk factors; Mutation analysis; SIDS; TSPYL1