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

Sanlaville, Damien; Etchevers, Heather C.; Gonzalès, Marie; Martinovic, Jéléna; Clément-Ziza, Mathieu; Delezoide, Anne‐Lise; Aubry, M. C.; Pelet, Anna; Chemouny, Sophie; Cruaud, Corinne; Audollent, Sophie; Esculpavit, Chantal; Goudefroye, Géraldine; Ozilou, Catherine; Fredouille, C.; Joyé, Nicole; Morichon-Delvallez, Nicole; Dumez, Yves; Weissenbach, Jean; Münnich, Arnold; Amiel, Jeanne; Encha‐Razavi, Férechté; Lyonnet, Stanislas; Vekemans, Michel; Attié‐Bitach, Tania

doi:10.1136/jmg.2005.036160

Cited by 203 publications

(212 citation statements)

References 29 publications

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“…Cerebellar hypoplasia has been reported in pre‐term CHARGE fetuses ( n = 11/39, 28%) (Becker et al, 2001; Legendre et al, 2012; Sanlaville et al, 2006) and in a cohort of patients with CHD7 mutations ( n = 7/20, 35%) (Yu et al, 2013). As a first step toward identifying structural brain abnormalities in Chd7 haploinsufficient mice in an unbiased manner, brains from 11 adult Chd7 gt/+ (HET) and 13 Chd7 +/+ wildtype (WT) littermate control mice were imaged by high resolution structural MRI.…”

Section: Resultsmentioning

confidence: 99%

“…Lin et al (1990) identified CNS anomalies in 55% ( n = 26/47) and Tellier et al (1998) in 79% ( n = 37/47) of CHARGE syndrome patients. Sanlaville et al (2006) reported CNS anomalies in 100% ( n = 10/10) and Legendre et al (2012) in 70% ( n = 29/40) of pre‐term fetuses with CHD7 mutations. Specific anomalies included hypoplasia of the olfactory bulbs and mild cerebellar vermis hypoplasia (Becker et al, 2001; Legendre et al, 2012; Sanlaville et al, 2006; Sanlaville & Verloes, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Sanlaville et al (2006) reported CNS anomalies in 100% ( n = 10/10) and Legendre et al (2012) in 70% ( n = 29/40) of pre‐term fetuses with CHD7 mutations. Specific anomalies included hypoplasia of the olfactory bulbs and mild cerebellar vermis hypoplasia (Becker et al, 2001; Legendre et al, 2012; Sanlaville et al, 2006; Sanlaville & Verloes, 2007). Structural MRI analysis of a small cohort of CHARGE syndrome patients with CHD7 mutations identified cerebellar vermis hypoplasia in 35% of patients, with evidence for abnormal foliation in 25% of patients (Yu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Neuroanatomical anomalies have been reported in CHARGE syndrome (Becker, Stiemer, Neumann, & Entezami, 2001; Bergman, Bocca, Hoefsloot, Meiners, & van Ravenswaaij‐Arts, 2011; Issekutz, Prasad, Smith, & Blake, 2005; Lin et al, 1990; Sanlaville et al, 2006; Sanlaville & Verloes, 2007; Tellier et al, 1998). Lin et al (1990) identified CNS anomalies in 55% ( n = 26/47) and Tellier et al (1998) in 79% ( n = 37/47) of CHARGE syndrome patients.…”

Section: Introductionmentioning

confidence: 99%

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Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

Whittaker

Kasah

Donovan

et al. 2017

American J of Med Genetics Pt C

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Mutations in the gene encoding the ATP dependent chromatin‐remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital‐urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio‐temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

Whittaker

Kasah

Donovan

et al. 2017

American J of Med Genetics Pt C

View full text Add to dashboard Cite

show abstract

“…Arhinencephaly is another common feature in CHARGE syndrome (Legendre et al, 2012; Sanlaville et al, 2006) that can be observed in imaging. The olfactory nerves may be hypo‐ or aplastic, usually in combination with olfactory sulcus effacement.…”

Section: Diagnostic Value Of Cranial Imagingmentioning

confidence: 99%

Guidelines in CHARGE syndrome and the missing link: Cranial imaging

Geus

Free

Verbist

et al. 2017

American J of Med Genetics Pt C

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“CHARGE syndrome” is a complex syndrome with high and extremely variable comorbidity. As a result, clinicians may struggle to provide accurate and comprehensive care, and this has led to the publication of several clinical surveillance guidelines and recommendations for CHARGE syndrome, based on both single case observations and cohort studies. Here we perform a structured literature review to examine all the existing advice. Our findings provide additional support for the validity of the recently published Trider checklist. We also identified a gap in literature when reviewing all guidelines and recommendations, and we propose a guideline for neuroradiological evaluation of patients with CHARGE syndrome. This is of importance, as patients with CHARGE are at risk for peri‐anesthetic complications, making recurrent imaging procedures under anesthesia a particular risk in clinical practice. However, comprehensive cranial imaging is also of tremendous value for timely diagnosis, proper treatment of symptoms and for further research into CHARGE syndrome. We hope the guideline for neuroradiological evaluation will help clinicians provide efficient and comprehensive care for individuals with CHARGE syndrome.

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Molecular Genetics of CHARGE Syndrome

Ravenswaaij-Arts

Hoefsloot

2012

Encyclopedia of Life Sciences

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Coloboma of the eye, heart defects, atresia of the nasal choanae, retardation of growth and/or development, genital abnormalities and ear abnormalities and deafness (CHARGE) syndrome is a highly variable, multiple congenital anomaly syndrome with an estimated prevalence of 1 in 17 000. The main features are hypoplasia of the semicircular canals, coloboma, choanal atresia, heart defects, hypogonadotropic hypogonadism, ear malformations, deafness, cranial nerve dysfunction and cleft/lip palate. The phenotype shows a remarkable variability that cannot be explained by different genotypes. In most patients a de novo autosomal dominant loss‐of‐function mutation of chromodomain helicase deoxyribonucleic acid (DNA)‐binding gene 7 ( CHD7 ) is found. The CHD protein family plays a role in transcription regulation by chromatin remodelling. Expression studies as well as studies in stem cells, neural crest cells and animal models have revealed that CHD7 has a tissue‐ and embryonic stage‐specific function in enhancer‐mediated transcription. The broad phenotypic spectrum involving many organ systems that is seen in CHD7 haploinsufficiency can be explained by cell type‐specific binding sites, protein complexes and target genes of CHD7. Key Concepts: CHARGE syndrome is a multiple congenital anomaly syndrome with a highly variable and broad clinical spectrum. CHARGE syndrome shows remarkable clinical overlap with other multiple congenital anomaly syndromes. In contrast, CHD7 mutations do not cause nonsyndromic congenital defects. CHD7 is the main causal gene in CHARGE syndrome and codes for a chromodomain protein. Chromodomain proteins are important during embryonic development. CHD7 has a function in enhancer‐mediated transcription. Both the expression of CHD7 and its binding sites to genomic enhancer regions are cell type‐ and embryonic stage‐dependent. CHD7 haploinsufficiency alters transcription of tissue‐specific target genes that are normally regulated by CHD7 or complexes in which CHD7 is involved. CHD7 plays an important role in neural crest cells and the interaction of the neural crest with other tissues. Investigation of overlapping phenotypes and converging molecular pathways gives insight into the pathogenesis.

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

Cited by 203 publications

References 29 publications

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

Guidelines in CHARGE syndrome and the missing link: Cranial imaging

Molecular Genetics of CHARGE Syndrome

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