ABSTRACT. Spondyloepiphyseal dysplasia (SED) is an autosomal dominant skeletal dysplasia characterized by short stature, abnormal epiphyses and flattened vertebral bodies. SED is mainly caused by mutations in the gene encoding the type II procollagen α-1 chain (COL2A1). We looked for mutations in COL2A1 in three unrelated Chinese families with SED. Putative mutations were confirmed by RFLP analysis. We identified three missense mutations (p.G504S, p.G801S and p.G1176V) located in the triple-helical domain; p.G801S and p.G1176V are novel mutations. The p.G504S mutation has been associated with diverse phenotypes in previous studies. Our study extends the mutation spectrum of SED and confirms a relationship between mutations in the COL2A1 gene and clinical findings of SED.

BackgroundThe meiotic program initiation pathway genes (CYP26B1, NANOS1 and STRA8) have been proposed to play key roles in spermatogenesis.ObjectiveTo elucidate the exact role of the genetic variants of the meiosis initiation genes in spermatogenesis, we genotyped the potential functional genetic variants of CYP26B1, NANOS1 and STRA8 genes, and evaluated their effects on spermatogenesis in our study population.Design, Setting, and ParticipantsIn this study, all subjects were volunteers from the affiliated hospitals of Nanjing Medical University between March 2004 and July 2009 (NJMU Infertile Study). Total 719 idiopathic infertile cases were recruited and divided into three groups according to WHO semen parameters: 201 azoospermia patients (no sperm in the ejaculate even after centrifugation), 155 oligozoospermia patients (sperm counts <20×106/ml) and 363 infertility/normozoospermia subjects (sperm counts >20×106/ml). The control group consisted of 383 subjects with normal semen parameters, all of which had fathered at least one child without assisted reproductive technologies.MeasurementsEight single nucleotide polymorphisms (SNPs) in CYP26B1, NANOS1 and STRA8 genes were determined by TaqMan allelic discrimination assay in 719 idiopathic infertile men and 383 healthy controls.Results and LimitationsThe genetic variant rs10269148 of STRA8 gene showed higher risk of spermatogenic impairment in the groups of abnormospermia (including azoospermia subgroup and oligozoospermia subgroup) and azoospermia than the controls with odds ratios and 95% confidence intervals of 2.52 (1.29–4.94) and 2.92 (1.41–6.06), respectively (P = 0.006, 0.002 respective). Notably, larger sample size studies and in vivo or in vitro functional studies are needed to substantiate the biological roles of these variants.ConclusionsOur results provided epidemiological evidence supporting the involvement of genetic polymorphisms of the meiotic program initiation genes in modifying the risk of azoospermia and oligozoospermia in a Han-Chinese population.

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