Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network

Genome Research

Volumn 26, Issue 4, 2016, Pages 474-485

  Chassaing, Nicolas ^a,b,c   Davis, Erica E ^c,d   McKnight, Kelly L ^d   Niederriter, Adrienne R ^d   Causse, Alexandre ^a,b   David, Véronique ^e,f   Desmaison, Annaïck ^b   Lamarre, Sophie ^g,h,i   Vincent Delorme, Catherine ^j   Pasquier, Laurent ^k   Coubes, Christine ^l   Lacombe, Didier ^m,n   Rossi, Massimiliano ^o,p   Dufier, Jean Louis ^q   Dollfus, Helene ^r   Kaplan, Josseline ^c   Katsanis, Nicholas ^d   Etchevers, Heather C ^b,s   Faguer, Stanislas ^c   Calvas, Patrick ^a,b,c  

^a CHU PURPAN   (France)

^b UNIVERSITÉ PAUL SABATIER   (France)

^c INSERM   (France)

^d DUKE UNIVERSITY MEDICAL CENTER   (United States)

^e UNIVERSITÉ DE RENNES 1   (France)

^f PONTCHAILLOU UNIVERSITY HOSPITAL   (France)

^g INSA   (France)

^h UMR792 INGÉNIERIE DES SYSTÈMES BIOLOGIQUES ET DES PROCÉDÉS   (France)

ⁱ CNRS   (France)

^j LILLE UNIVERSITY HOSPITAL   (France)

^k SERVICE DE RHUMATOLOGIE   (France)

^l HÔPITAL ARNAUD DE VILLENEUVE   (France)

^m HÔPITAL PELLEGRIN   (France)

ⁿ UNIVERSITÉ DE BORDEAUX   (France)

^o HOSPICES CIVILS DE LYON   (France)

^p LYON NEUROSCIENCE RESEARCH CENTER   (France)

^q HÔPITAL NECKER ENFANTS MALADES   (France)

^r UNIVERSITY HOSPITAL OF STRASBOURG   (France)

^s AIX MARSEILLE UNIVERSITY   (France)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CRISPR ASSOCIATED PROTEIN; PROTEIN PATCHED 1; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR SOX2; TRANSCRIPTION FACTOR SOX;

ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DEVELOPMENTAL DISORDER; EMBRYO; EYE DEVELOPMENT; FRAMESHIFT MUTATION; GENE EXPRESSION; GENE LOCUS; HIGH THROUGHPUT SEQUENCING; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MICROPHTHALMIA; MISSENSE MUTATION; NONHUMAN; OCULAR DEVELOPMENTAL ANOMALY; PATHOGENICITY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BINDING; REGULATORY MECHANISM; TRANSCRIPTOMICS; ZEBRA FISH; ALLELE; ANIMAL; CASE CONTROL STUDY; DISEASE MODEL; DNA SEQUENCE; EYE MALFORMATION; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORK; GENETICS; HETEROZYGOTE; METABOLISM; MUTATION;

ALLELES; ANIMALS; CASE-CONTROL STUDIES; DISEASE MODELS, ANIMAL; EYE ABNORMALITIES; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORKS; GENETIC LOCI; HETEROZYGOTE; HUMANS; MUTATION; PATCHED-1 RECEPTOR; PHENOTYPE; SEQUENCE ANALYSIS, DNA; SOXB1 TRANSCRIPTION FACTORS; ZEBRAFISH;

EID: 84964056070     PISSN: 10889051     EISSN: 15495469     Source Type: Journal    
DOI: 10.1101/gr.196048.115     Document Type: Article

References (68)

1. The 1000 Genomes Project Consortium. 2015. A global reference for human genetic variation. Nature 526:68-74.
2. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR. 2010. A method and server for predicting damaging missense mutations. Nat Methods 7:248-249.
3. Bailey EC, Zhou L, Johnson RL. 2003. Several human PATCHED1 mutations block protein maturation. Cancer Res 63:1636-1638.
4. Bakrania P, Efthymiou M, Klein JC, Salt A, Bunyan DJ, Wyatt A, Ponting CP, Martin A, Williams S, Lindley V, et al. 2008. Mutations in BMP4 cause eye, brain, and digit developmental anomalies: overlap between the BMP4 and hedgehog signaling pathways. Am J Hum Genet 82:304-319.
5. Bakrania P, Ugur Iseri SA, Wyatt AW, Bunyan DJ, Lam WW, Salt A, Ramsay J, Robinson DO, Ragge NK. 2010. Sonic hedgehog mutations are an uncommon cause of developmental eye anomalies. Am J Med Genet A 152 A: 1310-1313.
6. Bermejo E, Martinez-Frias ML. 1998. Congenital eye malformations: clinical-epidemiological analysis of 1, 124, 654 consecutive births in Spain. Am J Med Genet 75:497-504.
7. Bibliowicz J, Gross JM. 2009. Expanded progenitor populations, vitreo-retinal abnormalities, and Müller glial reactivity in the zebrafish leprechaun/patched2 retina. BMC Dev Biol 9:52.
8. Bree AF, Shah MR. 2011. Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS). Am J Med Genet A 155 A: 2091-2097.
9. Bumcrot DA, McMahon AP. 1995. Somite differentiation. Sonic signals somites. Curr Biol 5:612-614.
10. Butterfield NC, Metzis V, McGlinn E, Bruce SJ, Wainwright BJ, Wicking C. 2009. Patched1is acrucial determinant of asymmetry and digit number in the vertebrate limb. Development 136:3515-3524.
11. Chassaing N, Vigouroux A, Calvas P. 2009. Mutations in the newly identified RAX regulatory sequence are not a frequent cause of micro/anophthalmia. Genet Test Mol Biomarkers 13:289-290.
12. Chassaing N, Causse A, Vigouroux A, Delahaye A, Alessandri JL, Boespflug-Tanguy O, Boute-Benejean O, Dollfus H, Duban-Bedu B, Gilbert-Dussardier B, et al. 2014. Molecular findings and clinical datainacohort of 150 patients with anophthalmia/microphthalmia. Clin Genet 86:326-334.
13. Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, Beachy PA. 1996. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383:407-413.
14. Chotteau-Lelievre A, Dolle P, Gofflot F. 2006. Expression analysis of murine genes using in situ hybridization with radioactive and nonradioactively labeled RNA probes. Methods Mol Biol 326:61-87.
15. Christiansen AE, Ding T, Bergmann A. 2012. Ligand-independent activation of the Hedgehog pathway displays non-cell autonomous proliferation during eye development in Drosophila. Mech Dev 129:98-108.
16. Danno H, Michiue T, Hitachi K, Yukita A, Ishiura S, Asashima M. 2008. Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression. Proc Natl Acad Sci 105:5408-5413.
17. De Stefano I, Tanno B, Giardullo P, Leonardi S, Pasquali E, Antonelli F, Tanori M, Casciati A, Pazzaglia S, Saran A, et al. 2015. The Patched 1 tumor-suppressor gene protects the mouse lens from spontaneous and radiation-induced cataract. Am J Pathol 185:85-95.
18. Fantes J, Ragge NK, Lynch SA, McGill NI, Collin JR, Howard-Peebles PN, Hayward C, Vivian AJ, Williamson K, van Heyningen V, et al. 2003. Mutations in SOX2 cause anophthalmia. Nat Genet 33:461-463.
19. Fares-Taie L, Gerber S, Chassaing N, Clayton-Smith J, Hanein S, Silva E, Serey M, Serre V, Gerard X, Baumann C, et al. 2013. ALDH1A3 mutations cause recessive anophthalmia and microphthalmia. Am J Hum Genet 92:265-270.
20. Ferda Percin E, Ploder LA, Yu JJ, Arici K, Horsford DJ, Rutherford A, Bapat B, Cox DW, Duncan AM, Kalnins VI, et al. 2000. Human microphthalmia associated with mutations in the retinal homeobox gene CHX10. Nat Genet 25:397-401.
21. Fu W, O'Connor TD, Jun. G, Kang HM, Abecasis G, Leal SM, Gabriel S, Rieder MJ, Altshuler D, Shendure J, eta l. 2013. Analysisof6, 515 exomes reveals the recent origin of most human protein-coding variants. Nature 493:216-220.
22. Goodrich LV, Johnson RL, Milenkovic L, McMahon JA, Scott MP. 1996. Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog. Genes Dev 10:301-312.
23. Hahn H, Wojnowski L, Zimmer AM, Hall J, Miller G, Zimmer A. 1998. Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome. Nat Med 4:619-622.
24. Hever AM, Williamson KA, van Heyningen V. 2006. Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2. Clin Genet 69:459-470.
25. Hime GR, Lada H, Fietz MJ, Gillies S, Passmore A, Wicking C, Wainwright BJ. 2004. Functional analysis in Drosophila indicates that the NBCCS/PTCH1 mutation G509V results in activation of smoothened through a dominant-negative mechanism. Dev Dyn 229:780-790.
26. The International HapMap 3 Consortium, Altshuler DM, Gibbs RA, Peltonen L, Altshuler DM, Gibbs RA, Peltonen L, Dermitzakis E, Schaffner SF, Yu F, et al. 2010. Integrating common and rare genetic variation in diverse human populations. Nature 467:52-58.
27. Jeong J, McMahon AP. 2005. Growth and pattern of the mammalian neural tube are governed by partially overlapping feedback activities of the hedgehog antagonists patched 1 and Hhip1. Development 132:143-154.
28. Kamachi Y, Uchikawa M, Tanouchi A, Sekido R, Kondoh H. 2001. Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development. Genes Dev 15:1272-1286.
29. Kamachi Y, Okuda Y, Kondoh H. 2008. Quantitative assessment of the knockdown efficiency of morpholino antisense oligonucleotides in zebrafish embryos using a luciferase assay. Genesis 46:1-7.
30. Karlstrom RO, Trowe T, Klostermann S, Baier H, Brand M, Crawford AD, Grunewald B, Haffter P, Hoffmann H, Meyer SU, et al. 1996. Zebrafish mutations affecting retinotectal axon pathfinding. Development 123:427-438.
31. Ko BS, Chang TC, Shyue SK, Chen YC, Liou JY. 2009. An efficient transfection method for mouse embryonic stem cells. Gene Ther 16:154-158.
32. Koudijs MJ, den Broeder MJ, Keijser A, Wienholds E, Houwing S, van Rooijen EM, Geisler R, van Eeden FJ. 2005. The zebrafish mutants dre, uki, and lep encode negative regulators of the hedgehog signaling pathway. PLoS Genetics 1:e19.
33. Koudijs MJ, den Broeder MJ, Groot E, van Eeden FJ. 2008. Genetic analysis of the two zebrafish patched homologues identifies novel roles for the hedgehog signaling pathway. BMC Dev Biol 8:15.
34. Kumar P, Henikoff S, Ng PC. 2009. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4:1073-1081.
35. Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Hoover J, et al. 2016. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res 44:D862-D868.
36. Lee J, Willer JR, Willer GB, Smith K, Gregg RG, Gross JM. 2008. Zebrafish blowout provides genetic evidence for Patched1-mediated negative regulation of Hedgehog signaling within the proximal optic vesicle of the vertebrate eye. Dev Biol 319:10-22.
37. Lee J, Cox BD, Daly CM, Lee C, Nuckels RJ, Tittle RK, Uribe RA, Gross JM. 2013. An ENU mutagenesis screen in zebrafish for visual system mutants identifies a novel splice-acceptor site mutation in patched2 that results in Colobomas. Invest Ophthalmol Vis Sci 53:8214-8221.
38. Li WH, Wu CI, Luo CC. 1984. Nonrandomness of point mutation as reflected in nucleotide substitutions in pseudogenes and its evolutionary implications. J Mol Evol 21:58-71.
39. Macdonald R, Barth KA, Xu Q, Holder N, Mikkola I, Wilson SW. 1995. Midline signalling is required for Pax gene regulation and patterning of the eyes. Development 121:3267-3278.
40. Mathelier A, Zhao X, Zhang AW, Parcy F, Worsley-Hunt R, Arenillas DJ, Buchman S, Chen CY, Chou A, Ienasescu H, et al. 2014. JASPAR 2014: an extensively expanded and updated open-access database oftranscription factor binding profiles. Nucleic Acids Res 42:D142-D147.
41. Ming JE, Kaupas ME, Roessler E, Brunner HG, Golabi M, Tekin M, Stratton RF, Sujansky E, Bale SJ, Muenke M. 2002. Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly. Hum Genet 110:297-301.
42. Nasrallah I, Golden JA. 2001. Brain, eye, and face defects as a result of ectopic localization of Sonic hedgehog protein in the developing rostral neural tube. Teratology 64:107-113.
43. Pasutto F, Sticht H, Hammersen G, Gillessen-Kaesbach G, Fitzpatrick DR, Nurnberg G, Brasch F, Schirmer-Zimmermann H, Tolmie JL, Chitayat D, et al. 2007. Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation. Am J Hum Genet 80:550-560.
44. Pasutto F, Mauri L, Popp B, Sticht H, Ekici A, Piozzi E, Bonfante A, Penco S, Schlotzer-Schrehardt U, Reis A. 2015. Whole exome sequencing reveals a novel de novo FOXC1 mutation in a patient with unrecognized Axenfeld-Rieger syndrome and glaucoma. Gene 568:76-80.
45. Pillai-Kastoori L, Wen W, Wilson SG, Strachan E, Lo-Castro A, Fichera M, Musumeci SA, Lehmann OJ, Morris AC. 2014. Sox11 is requiredtomaintain proper levels of Hedgehog signaling during vertebrate ocular morphogenesis. PLoS Genet 10:e1004491.
46. Pineda-Alvarez DE, Solomon BD, Roessler E, Balog JZ, Hadley DW, Zein WM, Hadsall CK, Brooks BP, Muenke M. 2011. A broad range of ophthalmologic anomalies is part of the holoprosencephaly spectrum. Am J Med Genet A 155 A: 2713-2720.
47. Putoux A, Thomas S, Coene KL, Davis EE, Alanay Y, Ogur G, Uz E, Buzas D, Gomes C, Patrier S, et al. 2011. KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes. Nat Genet 43:601-606.
48. Ragge NK, Brown AG, Poloschek CM, Lorenz B, Henderson RA, Clarke MP, Russell-Eggitt I, Fielder A, Gerrelli D, Martinez-Barbera JP, et al. 2005a. Heterozygous mutations of OTX2 cause severe ocular malformations. Am J Hum Genet 76:1008-1022.
49. Ragge NK, Salt A, Collin JR, Michalski A, Farndon PA. 2005b. Gorlin syndrome: The PTCH gene links ocular developmental defects and tumour formation. Br J Ophthalmol 89:988-991.
50. Reis LM, Semina EV. 2011. Genetics of anterior segment dysgenesis disorders. Curr Opin Ophthalmol 22:314-324.
51. Ribeiro LA, Murray JC, Richieri-Costa A. 2006. PTCH mutations in four Brazilian patients with holoprosencephaly and in one with holoprosencephaly-like features and normal MRI. Am J Med Genet A 140:2584-2586.
52. Roessler E, Du YZ, Mullor JL, Casas E, Allen WP, Gillessen-Kaesbach G, Roeder ER, Ming JE, Ruiz i Altaba A, Muenke M. 2003. Loss-of-function mutations in the human GLI2 gene are associated with pituitary anomalies and holoprosencephaly-like features. Proc Natl Acad Sci 100:13424-13429.
53. Schauerte HE, van Eeden FJ, Fricke C, Odenthal J, Strahle U, Haffter P. 1998. Sonic hedgehog is not required for the induction of medial floor plate cells in the zebrafish. Development 125:2983-2993.
54. Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K. 2001. dbSNP: the NCBI database ofgenetic variation. Nucleic Acids Res 29:308-311.
55. Slavotinek AM. 2011. Eye development genes and known syndromes. Mol Genet Metab 104:448-456.
56. Srour M, Chitayat D, Caron V, Chassaing N, Bitoun P, Patry L, Cordier MP, Capo-Chichi JM, Francannet C, Calvas P, et al. 2013. Recessive and dominant mutations in retinoic acid receptor β in cases with microphthalmia and diaphragmatic hernia. Am J Hum Genet 93:765-772.
57. Tabata Y, Ouchi Y, Kamiya H, Manabe T, Arai K, Watanabe S. 2004. Specification of the retinal fate of mouse embryonic stem cells by ectopic expression of Rx/rax, a homeobox gene. Mol Cell Biol 24:4513-4521.
58. Takabatake Y, Takabatake T, Sasagawa S, Takeshima K. 2002. Conserved expression control and shared activity between cognate T-box genes Tbx2 and Tbx3 in connection with Sonic hedgehog signaling during Xenopus eye development. Dev Growth Differ 44:257-271.
59. Tay SY, Ingham PW, Roy S. 2005. A homologue of the Drosophila kinesinlike protein Costal2 regulates Hedgehog signal transduction in the vertebrate embryo. Development 132:625-634.
60. Varga ZM, Amores A, Lewis KE, Yan YL, Postlethwait JH, Eisen JS, Westerfield M. 2001. Zebrafish smoothened functions in ventral neural tube specification and axon tract formation. Development 128:3497-3509.
61. Verma AS, Fitzpatrick DR. 2007. Anophthalmia and microphthalmia. Orphanet J Rare Dis 2:47.
62. Villavicencio EH, Walterhouse DO, Iannaccone PM. 2000. The Sonic hedgehog-Patched-Gli pathway in human development and disease. Am J Hum Genet 67:1047-1054.
63. Weh E, Reis LM, Happ HC, Levin AV, Wheeler PG, David KL, Carney E, Angle B, Hauser N, Semina EV. 2014. Whole exome sequence analysis of Peters anomaly. Hum Genet 133:1497-1511.
64. Weiss AH, Kousseff BG, Ross EA, Longbottom J. 1989. Simple microphthalmos. Arch Ophthalmol 107:1625-1630.
65. Wolff C, Roy S, Ingham PW. 2003. Multiple muscle cell identities induced by distinct levels and timing of hedgehog activity in the zebrafish embryo. Curr Biol 13:1169-1181.
66. Yamamoto Y, Stock DW, Jeffery WR. 2004. Hedgehog signalling controls eye degeneration in blind cavefish. Nature 431:844-847.
67. Zhang R, Huang H, Cao P, Wang Z, Chen Y, Pan Y. 2013. Sma- and Mad-related protein 7 (Smad7) is required for embryonic eye development in the mouse. J Biol Chem 288:10275-10285.
68. Zhao L, Zevallos SE, Rizzoti K, Jeong Y, Lovell-Badge R, Epstein DJ. 2012. Disruption of SoxB1-dependent Sonic hedgehog expression in the hypothalamus causes septo-optic dysplasia. Dev Cell 22:585-596.