The Monique and Jacques Roboh

Department of

Genetic Research

The Roboh Department of Genetic Research is equipped with advanced equipment for genomic chip analysis.  The major application of this technology is in the identification of disease causing genes in patients with undiagnosed conditions. This is an immense task as the DNA consists of three billion bases.  Finding the disease-causing mutation in a single base is like picking an incorrect telephone number in one out of 30,000 telephone books.  So far, we have been able to identify 15 new disease causing genes. In most cases, the parents of the patients originated (at least partly) from the same ethnic background.

Over 50 on-going projects are being held in the department, in different stages of processing.  New projects are initiated by physicians or by the patients themselves, from Israel and from abroad, and are being funded by the medical insurances or by the research funds of the department researchers.

References

1. Miller C,  Saada A, Shaul N, Shabtai N, Ben-Shalom E, Shaag A, Hershkovitz E, Elpeleg O. (2004). Defective mitochondrial translation due to a ribosomal protein (MRPS16) mutation. Ann Neurol 56:734-8 

2. Elpeleg O, Miller C, Hershkovitz E, Bitner-Glindzicz M, Bondi-Rubinstein G, Rahman S, Pagnamenta A, Eshhar S , Saada A. (2005). Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion. Am J Hum Genet 76:1081-6.

3. Smeitink JA, Elpeleg O, Antonicka H, Diepstra H, Saada A, Smits P, Sasarman F, Vriend G, Jacob-Hirsch J, Shaag A, Rechavi G, Welling B, Horst J, Rodenburg RJ, van den Heuvel B, Shoubridge EA. (2006) Distinct clinical phenotypes associated with a mutation in the mitochondrial translation elongation factor EFTs. Am J Hum Genet. 79:869-77.

4. Edvardson S, Shaag A, Kolesnikova O, Gomori JM, Tarassov I, Einbinder T, Saada A, Elpeleg O. (2007) Deleterious mutation in the mitochondrial arginyl–transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. Am J Hum Genet 81;857-862.

5. Saada A, Shaag A, Arnon S, Dolfin T, Miller C, Fuchs-Telem D, Lombes A, Elpeleg O. (2007) Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation. J Med Genet 44:784-786

6. Saada A, Edvardson S, Rapoport M, Shaag A, Amry K, Miller C, Lorberboum-Galski H, Elpeleg O. (2008) C6ORF66 is a novel assembly factor of mitochondrial complex I. Am J Hum Genet. 82:32-8

7. Barghuti F, Elian K, Gomori JM, Shaag A, Edvardson S, Saada A, Elpeleg O. (2008) The unique neuroradiology of complex I deficiency due to NDUFA12L defect. Mol Genet Metab 94:78-82

8. Berger I, Hershkovitz E, Shaag A, Edvardson S, Saada A, Elpeleg O. (2008) Mitochondrial complex I deficiency due to a deleterious NDUFA11 mutation. Ann Neurol 63:405-8.

9. Ghezzi D, Saada A, D'Adamo P, Fernandez-Vizarra E, Gasparini P, Tiranti V, Elpeleg O, Zeviani M. (2008) FASTKD2 nonsense mutation in an infantile mitochondrial encephalomyopathy associated with cytochrome c oxidase deficiency. Am J Hum Genet 83:415-23

10. Zeharia A, Shaag A, Houtkooper RH, Hindi T, de Lonlay P, Erez G, Hubert L, Saada A, de Keyzer Y, Eshel G, Vaz FM, Pines O, Elpeleg O. (2008) Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood. Am J Hum Genet 83:489-94

11. Molho-Pessach V, Lerer I, Abeliovich D, Agha Z, Abu Libdeh A, Broshtilova V, Elpeleg O, Zlotogorski A. (2008) The H syndrome is caused by mutations in the nucleoside transporter hENT3. Am J Hum Genet 83:529-34

12. Edvardson S, Hama H, Shaag A, Gomori JM, Berger I, Soffer D, Korman SH, Taustein I, Saada A, Elpeleg O. (2008) Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia. Am J Hum Genet 83:643-8.

13. Spiegel R, Shaag A, Mandel H, Reich D, Penyakov M, Hujeirat Y, Saada A, Elpeleg O, Shalev SA. (2009) Mutated NDUFS6 is the cause of fatal neonatal lactic acidemia in Caucasus Jews. Eur J Hum Genet. 17:1200-3.

14. Shteyer E, Saada A, Shaag A, Al-Hijawi FA, Kidess R, Revel-Vilk S, Elpeleg O. (2009) Exocrine pancreatic insufficiency, dyserythropoeitic anemia, and calvarial hyperostosis are caused by a mutation in the COX4I2 gene. Am J Hum Genet. 84:412-7.

15. Zeharia A, Shaag A, Pappo O, Mager-Heckel AM, Saada A, Beinat M, Karicheva O, Mandel H, Ofek N, Segel R, Marom D, Rötig A, Tarassov I, Elpeleg O. (2009) Acute infantile liver failure due to mutations in the TRMU gene. Am J Hum Genet 85:401-7.

16. Spiegel R, Shaag A, Edvardson S, Mandel H, Stepensky P, Shalev SA, Horovitz Y, Pines O, Elpeleg O. (2009) SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis. Ann Neurol 66:419-24.

17. Edvardson S, Shaag A, Zenvirt S, Shanske AL, Gomori JM, Erlich Y, Hannon GJ, Ekstein J, Elpeleg O. (2010) Joubert syndrome (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation. Am J Hum Genet.  86:93-97.