Alternative titles; symbols
HGNC Approved Gene Symbol: SARDH
SNOMEDCT: 64852002; ICD10CM: E72.59;
Cytogenetic location: 9q34.2 Genomic coordinates (GRCh38): 9:133,659,418-133,739,955 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 9q34.2 | [Sarcosinemia] | 268900 | Autosomal recessive | 3 |
Sarcosine dehydrogenase (SARDH; EC 1.5.99.1) is a liver mitochondrial matrix flavoenzyme that catalyzes the oxidative demethylation of sarcosine (summary by Eschenbrenner and Jorns, 1999).
By homology searching, Eschenbrenner and Jorns (1999) identified a partial human infant brain SARDH cDNA. Using this partial cDNA, they isolated a full-length human liver cDNA. The predicted 918-amino acid SARDH protein contains a putative 22-amino acid mitochondrial targeting sequence, an ADP-binding site, and a stretch of 12 amino acids that matches the covalent flavin-containing peptide from rat liver Sardh. Human SARDH shares 89% amino acid sequence identity with rat liver Sardh and 34% identity with rat liver dimethylglycine dehydrogenase. Northern blot analysis of various human adult and fetal tissues detected a 4-kb SARDH transcript at high levels in adult and fetal liver and at lower levels in adult pancreas and kidney and fetal kidney. Eschenbrenner and Jorns (1999) identified cDNAs corresponding to alternatively spliced and polyadenylated SARDH transcripts.
Eschenbrenner and Jorns (1999) determined that the SARDH gene spans at least 75.3 kb and contains 21 exons.
Eschenbrenner and Jorns (1999) identified 3 genomic sequences from 9q34 that contain the SARDH gene. The localization of the human SARDH gene to 9q34 is consistent with genetic studies using a mouse model for sarcosinemia that mapped the mouse Sardh gene to a region of chromosome 2 that shows homology of synteny with human 9q33-q34 (Harding et al., 1992; Brunialti et al., 1996).
In 4 individuals from 3 consanguineous Israeli Arab families and 3 individuals from 3 French families who had elevated levels of sarcosine in blood and urine (SARCOS; 268900), Bar-joseph et al. (2012) sequenced the SARDH gene and identified homozygous or compound heterozygous mutations in 3 families (604455.0001-604455.0004). In 1 French family, they found a uniparental disomy in the region of the SARDH gene. No mutation in the SARDH gene was found in 2 of the Israeli Arab families, suggesting genetic heterogeneity.
In 2 Israeli Arab sisters with elevated levels of sarcosine in blood and urine (SARCOS; 268900), whose parents were first cousins, Bar-joseph et al. (2012) sequenced the SARDH gene and identified a homozygous 211G-T transversion resulting in a val71-to-phe (V71F) substitution at a conserved residue.
In a French Canadian individual with elevated levels of sarcosine in blood and urine (SARCOS; 268900), Bar-joseph et al. (2012) sequenced the SARDH gene and identified a homozygous 860C-T transition resulting in a pro287-to-leu (P287L) substitution at a conserved residue.
In an individual of German and French ancestry who had elevated levels of sarcosine in blood and urine (SARCOS; 268900), Bar-joseph et al. (2012) sequenced the SARDH gene and identified compound heterozygous mutations: a 2167C-T transition resulting in an arg723-to-ter (R723X) substitution, and a 1540C-T transition resulting in an arg514-to-ter (R514X) substitution (604455.0004).
For discussion of the arg514-to-ter (R514X) mutation in the SARDH gene that was found in compound heterozygous state in a patient with elevated levels of sarcosine in blood and urine (SARCOS; 268900) by Bar-joseph et al. (2012), see 604455.0003.
Bar-joseph, I., Pras, E., Reznik-Wolf, H., Marek-Yagel, D., Abu-Horvitz, A., Dushnitzky, M., Goldstein, N., Rienstein, S., Dekel, M., Pode-Shakked, B., Zlotnik, J., Benarrosh, A., Gillery, P., Hofliger, N., Auray-Blais, C., Garnotel, R., Anikster, Y. Mutations in the sarcosine dehydrogenase gene in patients with sarcosinemia. Hum. Genet. 131: 1805-1810, 2012. [PubMed: 22825317] [Full Text: https://doi.org/10.1007/s00439-012-1207-x]
Brunialti, A. L. B., Harding, C. O., Wolff, J. A., Guenet, J.-L. The mouse mutation sarcosinemia (sar) maps to chromosome 2 in a region homologous to human 9q33-q34. Genomics 36: 182-184, 1996. [PubMed: 8812433] [Full Text: https://doi.org/10.1006/geno.1996.0442]
Eschenbrenner, M., Jorns, M. S. Cloning and mapping of the cDNA for human sarcosine dehydrogenase, a flavoenzyme defective in patients with sarcosinemia. Genomics 59: 300-308, 1999. [PubMed: 10444331] [Full Text: https://doi.org/10.1006/geno.1999.5886]
Harding, C. O., Williams, P., Pflanzer, D. M., Cowell, R. E., Lyne, P. W., Wolff, J. A. sar: a genetic mouse model for human sarcosinemia generated by ethylnitrosourea mutagenesis. Proc. Nat. Acad. Sci. 89: 2644-2648, 1992. [PubMed: 1372986] [Full Text: https://doi.org/10.1073/pnas.89.7.2644]