• PMID: 17848414
• Gene Name: GRTH
• Condition: Azoospermia, male infertility
• Association: The Arg(242)His missense mutation of the GRTH/DDX25 gene associated with expression of a protein with reduced basicity, and the absence of the phospho-GRTH species, could be of relevance to some of the functional aspects of the protein that impact on germ
• Mutation: R242H in exon 8, silent mutation in exon11
• Population size: 243
• Population details: 243 (143 NOA, 100 fertile Japanese men)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: GRTH, DDX25
• Other associated phenotypes: Azoospermia, male infertility

Polymorphism of the GRTH/DDX25 gene in normal and infertile Japanese men: a missense mutation associated with loss of GRTH phosphorylation

Tsai-Morris CH, Koh E, Sheng Y, Maeda Y, Gutti R, Namiki M, Dufau ML.

The gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is present in Leydig and germ cells of rodents, and is essential for fertility in mice. This study evaluated the incidence of GRTH/DDX25 gene mutations in a group of infertile patients with non-obstructive azoospermia (NOA), 85% with a preponderance of Sertoli cells in the seminiferous tubule and 15% with spermatogenic arrest, and compared them to a group of fertile subjects. Exonic sequences in the GRTH gene were screened using denaturing high-performance liquid chromatography of the genomic DNA from 143 NOA and 100 fertile Japanese men. A unique heterozygous missense mutation Arg(242)His in exon 8 was identified in 5.8% of Sertoli cell-only patients and in 1% of normal subjects. Although the mutant protein was efficiently expressed in COS-1 cells, only the 56 kDa nuclear/cytoplasmic non-phosphorylated species was present, whereas the 61 kDa cytosolic phosporylated species was absent. In addition, a silent mutation was identified in exon 11 in NOA subjects. The Arg(242)His missense mutation of the GRTH/DDX25 gene associated with expression of a protein with reduced basicity, and the absence of the phospho-GRTH species, could be of relevance to some of the functional aspects of the protein that impact on germ cell development and/or function. FAU - Tsai-Morris, Chon-Hwa AU - Tsai-Morris CH AD - Section on Molecular Endocrinology, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, MD 20892, USA. FAU - Koh, Eitetsu AU - Koh E FAU - Sheng, Yi AU - Sheng Y FAU - Maeda, Yuji AU - Maeda Y FAU - Gutti, Ravi AU - Gutti R FAU - Namiki, Mikio AU - Namiki M