title: Detection of a mutation in the intron of Sperm-specific glyceraldehyde-3-phosphate dehydrogenase gene in patients with fibrous sheath dysplasia of the sperm flagellum.
abstract: The fibrous sheath is a unique cytoskeletal structure surrounding the axoneme and outer dense fibres of the sperm flagellum. Dysplasia of the fibrous sheath (DFS) is a defect of spermatozoa observed in severe asthenozoospermic patients and characterised by morphologically abnormal flagella with distorted fibrous sheaths. Sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDS) is a glycolytic enzyme that is tightly associated with the fibrous sheath of the sperm flagellum. The enzymatic activity of GAPDS was investigated in sperm samples of seven patients with DFS and compared to that of normal spermatozoa (n = 10). The difference in GAPDS activity in DFS and normal spermatozoa was statistically significant (0.19 ± 0.11 and 0.75 ± 0.11 μmol NADH per min per mg protein respectively). Immunochemical staining revealed irregular distribution of GAPDS in the flagellum of DFS spermatozoa. Other five samples with typical alterations in the fibrous sheath were assayed for mutations within human GAPDS gene. In all five cases, a replacement of guanine by adenine was revealed in the intron region between the sixth and the seventh exons of GAPDS. It is assumed that the deficiency in GAPDS observed in most DFS sperm samples is ascribable to a disorder in the regulation of GAPDS expression caused by the mutation in the intron region of GAPDS gene.
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Moscow state University, Moscow, Russia.
authors.forename: Y L
authors.initials: YL
authors.lastname: Elkina
authors.affiliation: Belozersky Institute of Physico-chemical biology, Moscow state University, Moscow, Russia.
authors.forename: M L
authors.initials: ML
authors.lastname: Kuravsky
authors.affiliation: Belozersky Institute of Physico-chemical biology, Moscow state University, Moscow, Russia.
authors.forename: E E
authors.initials: EE
authors.lastname: Bragina
authors.affiliation: Federal State Budgetary Institution "Research Centre for Medical Genetics", Moscow, Russia.
authors.forename: L F
authors.initials: LF
authors.lastname: Kurilo
authors.affiliation: Federal State Budgetary Institution "Research Centre for Medical Genetics", Moscow, Russia.
authors.forename: S S
authors.initials: SS
authors.lastname: Khayat
authors.affiliation: Belozersky Institute of Physico-chemical biology, Moscow state University, Moscow, Russia.
authors.forename: M Y
authors.initials: MY
authors.lastname: Sukhomlinova
authors.affiliation: Belozersky Institute of Physico-chemical biology, Moscow state University, Moscow, Russia.
authors.forename: E V
authors.initials: EV
authors.lastname: Schmalhausen
mesh_terms: D053627:Asthenozoospermia / Q000235:genetics*; D003599:Cytoskeleton / Q000378:metabolism; D004252:DNA Mutational Analysis; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D008854:Microscopy, Electron; D009154:Mutation; D012426:Russia; D013081:Sperm Motility / Q000235:genetics*; D013082:Sperm Tail / Q000648:ultrastructure*; D013094:Spermatozoa / Q000002:abnormalities* / Q000648:ultrastructure
chemical_list: C579041:GAPDHS protein, human; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
keywords: Asthenozoospermia; fibrous sheath dysplasia; sperm-specific glyceraldehyde-3-phosphate dehydrogenase; spermatozoa