The Danek Gartner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel.
Hum Genet. 2012 Nov;131(11):1805-10. doi: 10.1007/s00439-012-1207-x. Epub 2012 Jul 24.
Sarcosinemia is an autosomal recessive metabolic trait manifested by relatively high concentrations of sarcosine in blood and urine. Sarcosine is a key intermediate in 1-carbon metabolism and under normal circumstances is converted to glycine by the enzyme sarcosine dehydrogenase. We encountered six families from two different descents (French and Arab), each with at least one individual with elevated levels of sarcosine in blood and urine. Using the "candidate gene approach" we sequenced the gene encoding sarcosine dehydrogenase (SARDH), which plays an important role in the conversion of sarcosine to glycine, and found four different mutations (P287L, V71F, R723X, R514X) in three patients. In an additional patient, we found a uniparental disomy in the region of SARDH gene. In two other patients, we did not find any mutations in this gene. We have shown for the first time that mutations in the SARDH gene are associated with sarcosinemia. In addition, our results indicate that other genes are most probably involved in the pathogenesis of this condition.
高丝氨酸血症是一种常染色体隐性遗传代谢病，其特征为血液和尿液中高丝氨酸浓度相对较高。丝氨酸是 1 碳代谢的关键中间产物，在正常情况下，丝氨酸被丝氨酸脱氢酶（sarcosine dehydrogenase，SARDH）酶转化为甘氨酸。我们共发现了来自两个不同血统（法国和阿拉伯）的六个家族，每个家族至少有一名个体的血液和尿液中丝氨酸水平升高。我们采用“候选基因方法”对编码丝氨酸脱氢酶（SARDH）的基因进行测序，该基因在丝氨酸转化为甘氨酸的过程中发挥着重要作用，结果在 3 名患者中发现了 4 种不同的突变（P287L、V71F、R723X、R514X）。在另一名患者中，我们发现 SARDH 基因区域存在单亲二体性。在另外 2 名患者中，我们未在该基因中发现任何突变。我们首次证明 SARDH 基因突变与高丝氨酸血症有关。此外，我们的结果表明，其他基因很可能也参与了这种疾病的发病机制。
