Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome - PubMed (original) (raw)

Review

Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome

Gabriel E Zentner et al. Am J Med Genet A. 2010 Mar.

Abstract

CHARGE syndrome [coloboma of the eye, heart defects, atresia of the choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities (including deafness)] is a genetic disorder characterized by a specific and a recognizable pattern of anomalies. De novo mutations in the gene encoding chromodomain helicase DNA binding protein 7 (CHD7) are the major cause of CHARGE syndrome. Here, we review the clinical features of 379 CHARGE patients who tested positive or negative for mutations in CHD7. We found that CHARGE individuals with CHD7 mutations more commonly have ocular colobomas, temporal bone anomalies (semicircular canal hypoplasia/dysplasia), and facial nerve paralysis compared with mutation negative individuals. We also highlight recent genetic and genomic studies that have provided functional insights into CHD7 and the pathogenesis of CHARGE syndrome.

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Figures

Figure 1

A schematic representation of the CHD7 protein. Domains are depicted approximately to scale.

Figure 2

A model for CHD7 function. CHD7 binds to enhancer elements in the presence of protein cofactors and facilitates looping of chromatin to bring the enhancer in close proximity with transcription start sites and allowing CHD7 and associated cofactors to modulate the transcriptional output of the gene.

References

1. Adams ME, Hurd EA, Beyer LA, Swiderski DL, Raphael Y, Martin DM. Defects in vestibular sensory epithelia and innervation in mice with loss of Chd7 function: implications for human CHARGE syndrome. J Comp Neurol. 2007;504(5):519–32. - PubMed
1. Alazami MA, Alzahrani F, Alkuraya FS. Expanding the “E” in CHARGE. Am J Med Genet A. 2008;146A(14):1890–1892. - PubMed
1. Aramaki M, Udaka T, Kosaki R, Makita Y, Okamoto N, Yoshihashi H, Oki H, Nanao K, Moriyama N, Oku S, Hasegawa T, Takahashi T, Fukushima Y, Kawame H, Kosaki K. Phenotypic spectrum of CHARGE syndrome with CHD7 mutations. J Pediatr. 2006;148(3):410–414. - PubMed
1. Arrington CB, Cowley BC, Nightingale DR, Zhou H, Brothman HR, Viskochil DH. Interstitial deletion 8q11.2-q13 with congenital anomalies of CHARGE association. Am J Med Genet A. 2005;133A(3):326–330. - PubMed
1. Asakura Y, Toyota Y, Muroya K, Kurosawa K, Fujita K, Aida N, Kawame H, Kosaki K, Adachi M. Endocrine and Radiological Studies in Patients with Molecularly Confirmed CHARGE Syndrome. J Clin Endocrinol Metab. 2008;93(3):920–924. - PubMed

Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome - PubMed (original) (raw)