Genomic analysis of Meckel-Gruber syndrome in Arabs reveals marked genetic heterogeneity and novel candidate genes

European Journal of Human Genetics

Volumn 21, Issue 7, 2013, Pages 762-768

  Shaheen, Ranad ^a   Faqeih, Eissa ^b   Alshammari, Muneera J ^a,c   Swaid, Abdulrahman ^d   Al Gazali, Lihadh ^e   Mardawi, Elham ^f   Ansari, Shinu ^a   Sogaty, Sameera ^g   Seidahmed, Mohammed Z ^f   Almotairi, Muhammed I ^a   Farra, Chantal ^h   Kurdi, Wesam ^a   Al Rasheed, Shatha ^d   Alkuraya, Fowzan S ^a,c,i  

^a KING FAISAL SPECIALIST HOSPITAL AND RESEARCH CENTER   (Saudi Arabia)

^b King Fahad Mobile Hospital   (Saudi Arabia)

^c KING KHALID UNIVERSITY HOSPITAL   (Saudi Arabia)

^d KING SAUD BIN ABDULAZIZ UNIVERSITY FOR HEALTH SCIENCES   (Saudi Arabia)

^e UNITED ARAB EMIRATES UNIVERSITY   (United Arab Emirates)

^f SECURITY FORCES HOSPITAL   (Saudi Arabia)

^g KING FAHAD GENERAL HOSPITAL   (Saudi Arabia)

^h AMERICAN UNIVERSITY OF BEIRUT   (Lebanon)

ⁱ ALFAISAL UNIVERSITY   (Saudi Arabia)

Author keywords

autozygome; ciliopathy; encephalocele; EVC2; EXOC4

Indexed keywords

EXOCYST;

ARAB; ARTICLE; ELLIS VAN CREVELD SYNDROME; EVC2 GENE; EXOME; FAMILY; GENE; GENE MUTATION; GENE REPLICATION; GENE SEQUENCE; GENETIC ANALYSIS; GENETIC HETEROGENEITY; HUMAN; JOUBERT SYNDROME; MECKEL SYNDROME; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; SEC8 GENE;

ARABS; CILIARY MOTILITY DISORDERS; ENCEPHALOCELE; EXOME; GENETIC ASSOCIATION STUDIES; GENETIC HETEROGENEITY; GENOME, HUMAN; HUMANS; MEMBRANE PROTEINS; MUTATION; POLYCYSTIC KIDNEY DISEASES; PROTEINS; SEQUENCE ANALYSIS, DNA; VESICULAR TRANSPORT PROTEINS;

EID: 84879414293     PISSN: 10184813     EISSN: 14765438     Source Type: Journal    
DOI: 10.1038/ejhg.2012.254     Document Type: Article

References (44)

1. Seller MJ: Phenotypic variation in Meckel syndrome. Clin Genet 1981; 20: 74-77.
2. Teebi AS, Teebi SA: Genetic diversity among the Arabs. Community Genet 2005; 8: 21-26.
3. Salonen R, Norio R: The Meckel syndrome in Finland: epidemiologic and genetic aspects. Am J Med Genet 1984; 18: 691-698.
4. Kyttala M, Tallila J, Salonen R et al: MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome. Nat Genet 2006; 38: 155-157.
5. Consugar MB, Kubly VJ, Lager DJ et al: Molecular diagnostics of Meckel-Gruber syndrome highlights phenotypic differences between MKS1 and MKS3. Hum Genet 2007; 121: 591-599.
6. Dawe HR, Smith UM, Cullinane AR et al: The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation. Hum Mol Genet 2007; 16: 173-186.
7. Valente EM, Logan CV, Mougou-Zerelli S et al: Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes. Nat Genet 2010; 42: 619-625.
8. Smith UM, Consugar M, Tee LJ et al: The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. Nat Genet 2006; 38: 191-196.
9. Baala L, Audollent S, Martinovic J et al: Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome. Am J Hum Genet 2007; 81: 170-179.
10. Frank V, den Hollander AI, Bruchle NO et al: Mutations of the CEP290 gene encoding a centrosomal protein cause Meckel-Gruber syndrome. Hum Mutat 2008; 29: 45-52.
11. Delous M, Baala L, Salomon R et al: The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nat Genet 2007; 39: 875-881.
12. Tallila J, Jakkula E, Peltonen L, Salonen R, Kestila M: Identification of CC2D2A as a Meckel syndrome gene adds an important piece to the ciliopathy puzzle. Am J Hum Genet 2008; 82: 1361-1367.
13. Shaheen R, Faqeih E, Seidahmed MZ et al: A TCTN2 mutation defines a novel Meckel Gruber syndrome locus. Hum Mutat 2011; 32: 573-578.
14. Hopp K, Heyer CM, Hommerding CJ et al: B9D1 is revealed as a novel Meckel syndrome (MKS) gene by targeted exon-enriched next-generation sequencing and deletion analysis. Hum Mol Genet 2011; 20: 2524-2534.
15. Nigg EA, Raff JW: Centrioles, centrosomes, and cilia in health and disease. Cell 2009; 139: 663-678.
16. Leitch CC, Zaghloul NA, Davis EE et al: Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome. Nat Genet 2008; 40: 443-448.
17. Edvardson S, Shaag A, Zenvirt S et al: Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation. Am J Hum Genet 2010; 86: 93-97.
18. Baala L, Romano S, Khaddour R et al: The Meckel-Gruber syndrome gene, MKS3, is mutated in Joubert syndrome. Am J Hum Genet 2007; 80: 186-194.
19. Otto EA, Tory K, Attanasio M et al: Hypomorphic mutations in meckelin (MKS3/TMEM67) cause nephronophthisis with liver fibrosis (NPHP11). J Med Genet 2009; 46: 663-670.
20. Coppieters F, Lefever S, Leroy BP, De Baere E: CEP290, a gene with many faces: mutation overview and presentation of CEP290base. Hum Mutat 2010; 31: 1097-1108.
21. Arts HH, Doherty D, van Beersum SE et al: Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome. Nat Genet 2007; 39: 882-888.
22. Gorden NT, Arts HH, Parisi MA et al: CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-associated basal body protein CEP290. Am J Hum Genet 2008; 83: 559-571.
23. Salonen R, Kestila M, Bergmann C: Clinical utility gene card for: Meckel syndrome. Eur J Hum Genet 2011; 19; e-pub ahead of print 2 February 2011; doi:10.1038/ejhg.2010.255.
24. Cohen Jr. MM, Lemire RJ: Syndromes with cephaloceles. Teratology 1982; 25: 161-172.
25. Huang L, Szymanska K, Jensen VL et al: TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone. Am J Hum Genet 2011; 89: 713-730.
26. Alazami AM, Alshammari MJ, Salih MA et al: Molecular characterization of Joubert syndrome in Saudi Arabia. Hum Mutat 2012; 33: 1423-1428.
27. Srour M, Schwartzentruber J, Hamdan FF et al: Mutations in C5ORF42 cause Joubert syndrome in the French Canadian population. Am J Hum Genet 2012; 90: 693-700.
28. Shamseldin HE, Alshammari M, Al-Sheddi T et al: Genomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes. J Med Genet 2012; 49: 234-241.
29. Abu Safieh L, Aldahmesh MA, Shamseldin H et al: Clinical and molecular characterisation of Bardet-Biedl syndrome in consanguineous populations: the power of homozygosity mapping. J Med Genet 2010; 47: 236-241.
30. Abu-Safieh L, Al-Anazi S, Al-Abdi L et al: In search of triallelism in Bardet-Biedl syndrome. EJHG 2012; 20: 420-427.
31. Aldahmesh MA, Khan AO, Mohamed JY et al: Genomic analysis of pediatric cataract in Saudi Arabia reveals novel candidate disease genes. Genet Med 2012.
32. Abu-Safieh L, Alrashed M, Anazi S et al: Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. Genome Res 2012; e-pub ahead of print 26 October 2012.
33. Shaheen R, Alazami AM, Alshammari MJ et al: Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation. J Med Genet 2012; 49: 630-635.
34. Shaheen R, Al-Dirbashi OY, Al-Hassnan ZN et al: Clinical, biochemical and molecular characterization of peroxisomal diseases in Arabs. Clin Genet 2011; 79: 60-70.
35. Shaheen R, Faqeih E, Sunker A et al: Recessive mutations in DOCK6, encoding the guanidine nucleotide exchange factor DOCK6, lead to abnormal actin cytoskeleton organization and Adams-Oliver syndrome. Am J Hum Genet 2011; 89: 328-333.
36. Aldahmesh MA, Mohamed JY, Alkuraya HS et al: Recessive mutations in ELOVL4 cause ichthyosis, intellectual disability, and spastic quadriplegia. Am J Hum Genet 2011; 89: 745-750.
37. Zohn IE, Li Y, Skolnik EY, Anderson KV, Han J, Niswander L: p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation. Cell 2006; 125: 957-969.
38. Blair HJ, Tompson S, Liu YN et al: Evc2 is a positive modulator of Hedgehog signalling that interacts with Evc at the cilia membrane and is also found in the nucleus. BMC Biol 2011; 9: 14.
39. Valencia M, Lapunzina P, Lim D et al: Widening the mutation spectrum of EVC and EVC2: ectopic expression of Weyer variants in NIH 3T3 fibroblasts disrupts Hedgehog signaling. Hum Mutat 2009; 30: 1667-1675.
40. Ruiz-Perez VL, Goodship JA: Ellis-van Creveld syndrome and Weyers acrodental dysostosis are caused by cilia-mediated diminished response to hedgehog ligands. Am J Med Genet C Semin Med Genet 2009; 151C: 341-351.
41. Kemperdick H, Ammermann M, Janssen F, Lange H, Moubayed P: [The differential diagnosis of the Meckel syndrome and the Ellis-van-Creveld syndrome with encepha-locele (author's transl)]. Klin Padiatr 1975; 187: 87-93.
42. Ganner A, Lienkamp S, Schafer T et al: Regulation of ciliary polarity by the APC/C. Proc Natl Acad Sci USA 2009; 106: 17799-17804.
43. Park TJ, Mitchell BJ, Abitua PB, Kintner C, Wallingford JB: Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells. Nat Genet 2008; 40: 871-879.
44. Dixon-Salazar TJ, Silhavy JL, Udpa N et al: Exome sequencing can improve diagnosis and alter patient management. Sci Transl Med 2012; 4: 138ra178.