title: Mutations in the sarcosine dehydrogenase gene in patients with sarcosinemia.
abstract: 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.
authors: The Danek Gartner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel.
authors: Ifat
authors: I
authors: Bar-joseph
authors: Elon
authors: E
authors: Pras
authors: Haike
authors: H
authors: Reznik-Wolf
authors: Dina
authors: D
authors: Marek-Yagel
authors: Almogit
authors: A
authors: Abu-Horvitz
authors: Maya
authors: M
authors: Dushnitzky
authors: Nurit
authors: N
authors: Goldstein
authors: Shlomit
authors: S
authors: Rienstein
authors: Michal
authors: M
authors: Dekel
authors: Ben
authors: B
authors: Pode-Shakked
authors: Joseph
authors: J
authors: Zlotnik
authors: Anelia
authors: A
authors: Benarrosh
authors: Philippe
authors: P
authors: Gillery
authors: Niklaus
authors: N
authors: Hofliger
authors: Christiane
authors: C
authors: Auray-Blais
authors: Roselyne
authors: R
authors: Garnotel
authors: Yair
authors: Y
authors: Anikster
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012521:Sarcosine / Q000097:blood; D050892:Sarcosine Dehydrogenase / Q000172:deficiency / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004247:DNA; C494395:SARDH protein, human; D050892:Sarcosine Dehydrogenase; D012521:Sarcosine