Phenotypic spectrum of CHARGE syndrome in fetuses with CHD7 truncating mutations correlates with expression during human development

Damien Sanlaville ¹, Heather C Etchevers ¹, Marie Gonzales ², Jelena Martinovic ¹, Mathieu Clément-Ziza ¹, Anne-Lise Delezoide ³, Marie-Cécile Aubry ⁴, Anna Pelet ⁴, Sophie Chemouny ⁴, Corinne Cruau ⁵, Sophie Audollent ¹, Chantal Esculpavit ¹, Geraldine Goudefroye ¹, Catherine Ozilou ¹, Catherine Fredouille ⁶, Nicole Joyé ⁶, Nicole Morichon-Delvallez ¹, Yves Dumez ⁴, Jean Weissenbach ⁵, Arnold Munnich ¹, Jeanne Amiel ¹, Férechté Encha-Razavi ¹, Stanislas Lyonnet ¹, Michel Vekemans ¹ and Tania Attié-Bitach ^1*

¹ INSERM U-393, Hôpital Necker-Enfants Malades, France
² Unit& de Foetopathologie, HINSERM U-393, Hôpitapital Saint Antoine
³ Service de Biologie du développement, HÔpital Robert Debré, France
⁴ Service d'Obstétrique, HÔpital Necker-Enfants Malades, France
⁵ Genoscope, Evry, France, France
⁶ Unit& de Foetopathologie, HINSERM U-393, Hôpitapital Saint Antoine, France

^* To whom correspondence should be addressed. E-mail: tania.attie{at}necker.fr.

Accepted 18 August 2005

Abstract

Introduction: The acronym CHARGE, coined by Pagon et al 1 refers to a non-random cluster of malformations first described by Hall et al 2 including Coloboma, Heart malformation, choanal Atresia, Retardation of growth and / or development, Genital anomalies, and Ear anomalies. This set of multiple congenital anomalies is frequent, despite rare patients with normal intelligence, and prognosis remains poor. Recently, CHD7 gene mutations have been identified in CHARGE patients; however the function of CHD7 during development remains unknown.

Methods: We therefore studied a series of 10 antenatal cases in whom the diagnosis was suspected, considering that a careful pathological description would shed light on the CHD7 function during development. We also performed in situ hybridization analysis of the CHD7 gene during early human development.

Results: The diagnosis was confirmed in all 10 fetuses by the identification of a CHD7 heterozygous truncating mutation. Such results allowed us to further refine the phenotypic spectrum of developmental anomalies resulting from CHD7 dysfunction.

Discussion: Interestingly, arhinencephaly and semi-circular canal agenesis were two constant features which do not belong to formal diagnostic criteria so far. Expression analysis of the CHD7 gene during early human development emphasized the role of CHD7 in the development of central nervous system, internal ear, neural crest of pharyngeal arches, and more generally showed a good correlation between specific CHD7 expression pattern and the developmental anomalies observed in CHARGE syndrome.

Keywords: CHARGE syndrome, CHD7 gene, development, gene expression pattern, human embryogenesis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Maas, N. M C, Van de Putte, T., Melotte, C., Francis, A., Schrander-Stumpel, C. T R M, Sanlaville, D., Genevieve, D., Lyonnet, S., Dimitrov, B., Devriendt, K., Fryns, J.-P., Vermeesch, J. R (2009). The C20orf133 gene is disrupted in a patient with Kabuki syndrome. BMJ Case Reports 2009: bcr0620091994-bcr0620091994 [Abstract] [Full Text]  
• Layman, W.S., McEwen, D.P., Beyer, L.A., Lalani, S.R., Fernbach, S.D., Oh, E., Swaroop, A., Hegg, C.C., Raphael, Y., Martens, J.R., Martin, D.M. (2009). Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome. Hum Mol Genet 18: 1909-1923 [Abstract] [Full Text]  
• Alasti, F, Van Camp, G (2009). Genetics of microtia and associated syndromes. J. Med. Genet. 46: 361-369 [Abstract] [Full Text]  
• Jyonouchi, S., McDonald-McGinn, D. M., Bale, S., Zackai, E. H., Sullivan, K. E. (2009). CHARGE (Coloboma, Heart Defect, Atresia Choanae, Retarded Growth and Development, Genital Hypoplasia, Ear Anomalies/Deafness) Syndrome and Chromosome 22q11.2 Deletion Syndrome: A Comparison of Immunologic and Nonimmunologic Phenotypic Features. Pediatrics 123: e871-e877 [Abstract] [Full Text]  
• Schnetz, M. P., Bartels, C. F., Shastri, K., Balasubramanian, D., Zentner, G. E., Balaji, R., Zhang, X., Song, L., Wang, Z., LaFramboise, T., Crawford, G. E., Scacheri, P. C. (2009). Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns. Genome Res 19: 590-601 [Abstract] [Full Text]  
• Fujita, K., Aida, N., Asakura, Y., Kurosawa, K., Niwa, T., Muroya, K., Adachi, M., Nishimura, G., Inoue, T. (2009). Abnormal Basiocciput Development in CHARGE Syndrome. Am. J. Neuroradiol. 30: 629-634 [Abstract] [Full Text]  
• Thomas, S., Thomas, M., Wincker, P., Babarit, C., Xu, P., Speer, M. C., Munnich, A., Lyonnet, S., Vekemans, M., Etchevers, H. C. (2008). Human neural crest cells display molecular and phenotypic hallmarks of stem cells. Hum Mol Genet 17: 3411-3425 [Abstract] [Full Text]  
• Blustajn, J., Kirsch, C.F.E., Panigrahy, A., Netchine, I. (2008). Olfactory Anomalies in CHARGE Syndrome: Imaging Findings of a Potential Major Diagnostic Criterion. Am. J. Neuroradiol. 29: 1266-1269 [Abstract] [Full Text]  
• Asakura, Y., Toyota, Y., Muroya, K., Kurosawa, K., Fujita, K., Aida, N., Kawame, H., Kosaki, K., Adachi, M. (2008). Endocrine and Radiological Studies in Patients with Molecularly Confirmed CHARGE Syndrome. J. Clin. Endocrinol. Metab. 93: 920-924 [Abstract] [Full Text]  
• Maas, N. M C, Van de Putte, T., Melotte, C., Francis, A., Schrander-Stumpel, C. T R M, Sanlaville, D., Genevieve, D., Lyonnet, S., Dimitrov, B., Devriendt, K., Fryns, J.-P., Vermeesch, J. R (2007). The C20orf133 gene is disrupted in a patient with Kabuki syndrome. J. Med. Genet. 44: 562-569 [Abstract] [Full Text]  
• (2006). Mutated Gene Is Associated with CHARGE Syndrome in Half of Cases. JWatch Pediatrics 2006: 8-8 [Full Text]  
• Wainwright, H C (2006). My approach to performing a perinatal or neonatal autopsy.. J. Clin. Pathol. 59: 673-680 [Abstract] [Full Text]