Abstract:
BACKGROUND:CHARGE syndrome is characterized by coloboma, heart defects, choanal atresia, growth retardation, genitourinary malformation and ear abnormalities. The chromodomain helicase DNA-binding protein 7 (CHD7) gene is the major cause of CHARGE syndrome and is inherited in an autosomal dominant manner. Currently, the phenotype spectrum of CHARGE syndrome in neonatal population remain elusive. We aimed to investigate the phenotype spectrum of neonatal patients suspected to have CHARGE syndrome with pathogenic or likely pathogenic variants in the CHD7 gene. METHODS:We pooled next-generation sequencing data from the Neonatal Birth Defects Cohort (NBDC, ClinicalTrials.gov Identifier: NCT02551081) in Children's Hospital of Fudan University. The pathogenicity of novel variants was analyzed by bioinformatic and genetic analyses. Clinical information collection, Sanger sequencing and follow-up interviews were performed when possible. Cranial MRI of these patients was performed, the volumes of different regions of the brain were analyzed. RESULTS:A total of 12 unrelated patients in our cohort were found with CHD7 variants. Eight patients received a firm clinical diagnosis of CHARGE syndrome (Bergmann criteria, Blake criteria, Verloes criteria and Hale criteria). Three patients did not match any diagnostic criteria, and no patients matched the Verloes criteria. Phenotype spectrum analysis found that feeding difficulty was the dominant feature among this neonatal cohort. Six novel variants in the CHD7 gene (Glu2408*, Lys651*, c.5607 + 1G > T, Leu373Val, Lys2005Asnfs*37 and Gln1991*) were identified, expanding the variant database of the CHD7 gene. Cranial MRI analysis revealed significant volume loss in cingulate gyrus, occipital lobe, and cerebellum and volume gain in the left medial and inferior temporal gyri anterior white matter parts. CONCLUSIONS:Based on a relatively unbiased neonatal cohort, we concluded that CHARGE syndrome and CHD7 gene variants should be suspected in newborns who have feeding difficulty, and one or more malformations. TRIAL REGISTRATION:Neonatal Birth Defects Cohort (NBDC, ClinicalTrials.gov identifier: NCT02551081 ).
journal_name
BMC Med Genetjournal_title
BMC medical geneticsauthors
Chen X,Yan K,Gao Y,Wang H,Chen G,Wu B,Qin Q,Yang L,Zhou Wdoi
10.1186/s12881-019-0813-zsubject
Has Abstractpub_date
2019-05-30 00:00:00pages
93issue
1issn
1471-2350pii
10.1186/s12881-019-0813-zjournal_volume
20pub_type
杂志文章abstract:BACKGROUND:Glucocorticoids have an important role in early growth and development. Glucocorticoid receptor gene polymorphisms have been identified that contribute to the variability in glucocorticoid sensitivity. We examined whether these glucocorticoid receptor gene polymorphisms are associated with growth in fetal an...
journal_title:BMC medical genetics
pub_type: 杂志文章
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更新日期:2010-03-03 00:00:00
abstract::The Framingham Heart Study, founded in 1948 to examine the epidemiology of cardiovascular disease in a small town outside of Boston, has become the worldwide standard for cardiovascular epidemiology. It is among the longest running, most comprehensively characterized multi-generational studies in the world. Such semin...
journal_title:BMC medical genetics
pub_type: 杂志文章
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journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-014-0106-5
更新日期:2014-10-14 00:00:00
abstract:BACKGROUND:Retinitis pigmentosa (RP), a clinically and genetically heterogeneous group of retinal degeneration disorders affecting the photoreceptor cells, is one of the leading causes of genetic blindness. Mutations in the photoreceptor-specific gene RP1 account for 3-10% of cases of autosomal dominant RP (adRP). Most...
journal_title:BMC medical genetics
pub_type: 杂志文章
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更新日期:2006-04-05 00:00:00
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pub_type: 杂志文章
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更新日期:2020-10-08 00:00:00
abstract:BACKGROUND:Single Nucleotide Polymorphisms (SNPs) identified in Genome Wide Association Studies (GWAS) have generally moderate association with related complex diseases. Accordingly, Multilocus Genetic Risk Scores (MGRSs) have been computed in previous studies in order to assess the cumulative association of multiple S...
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journal_title:BMC medical genetics
pub_type: 杂志文章
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更新日期:2006-08-17 00:00:00
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更新日期:2016-07-11 00:00:00
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journal_title:BMC medical genetics
pub_type: 杂志文章
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更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Multiple endocrine neoplasia type 1 (MEN1) syndrome is usually accompanied by endocrine tumors, but non-endocrine tumors can occur as well. However, the coexistence of MEN1 syndrome and malignant tumor such as low-grade fibromyxoid sarcoma has not been described in the literature. Moreover, the MEN1 gene mut...
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pub_type: 杂志文章
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更新日期:2020-09-29 00:00:00
abstract:BACKGROUND:The Framingham Heart Study (FHS) recently obtained initial results from the first genome-wide association scan for renal traits. The study of 70,987 single nucleotide polymorphisms (SNPs) in 1,010 FHS participants provides a list of SNPs showing the strongest associations with renal traits which need to be v...
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pub_type: 杂志文章
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更新日期:2008-06-03 00:00:00
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pub_type: 杂志文章
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更新日期:2008-04-02 00:00:00
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更新日期:2009-06-10 00:00:00
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更新日期:2010-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1186/s12881-017-0404-9
更新日期:2017-05-03 00:00:00
abstract:BACKGROUND:Bone morphogenetic protein 4 gene (BMP4) plays a key role during maxillofacial development, since orofacial clefts are observed in animals when this gene is conditionally inactivated. We recently reported the existence of association between nonsyndromic cleft lip/palate (NSCLP) and BMP4 polymorphisms by det...
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更新日期:2011-12-19 00:00:00
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pub_type: 杂志文章,meta分析
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更新日期:2019-12-10 00:00:00
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pub_type: 杂志文章
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更新日期:2008-07-03 00:00:00
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pub_type: 杂志文章
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更新日期:2016-10-12 00:00:00
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journal_title:BMC medical genetics
pub_type: 杂志文章
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更新日期:2018-02-13 00:00:00
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更新日期:2017-03-24 00:00:00
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pub_type: 杂志文章
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更新日期:2019-11-21 00:00:00
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pub_type: 杂志文章
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更新日期:2008-05-06 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2013-01-23 00:00:00
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