Mutation Analysis in Chinese Patients with Cornelia de Lange Syndrome

Zhong, Qiulian; Liu, Jing; Xue, Jinjie; Wu, Lingqian

doi:10.1089/gtmb.2011.0383

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…(3) RT-PCR revealed a splicing mutation in exon 38, generating both normal transcript and an aberrant alternatively spliced transcript with exon 38 deletion. Detail information of the molecular study of these 4 patients has been published elsewhere in 2012 [ 10 ].…”

Section: Resultsmentioning

confidence: 99%

Clinical and genetic study of 20 patients from China with Cornelia de Lange syndrome

Hei

Gao²,

2018

BMC Pediatr

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BackgroundCornelia de Lange syndrome (CdLS) is a rare congenital syndrome with no racial difference. The objective of this study is to report the clinical characteristics and genetic study of 20 CdLS cases from China.MethodsThis is an observational study. Suspected patients were referred for further confirmation, clinical treatment, and genetic testing under voluntary condition. Demographic data and family history, data of clinical manifestations including facial dysmorphism and developmental delay of each patient were collected. Chromosomal analysis and NIPBL/SMC1A/SMC3 gene mutational analysis were carried out by PCR, reverse transcription PCR direct sequencing in the probands, and SNP array to detect the genome-wide copy number variations.ResultsTwenty CdLS cases from China were included in this study. Facial dysmorphisms, feeding difficulties, and developmental delay were the major clinical manifestations. Seven patients underwent gene mutation tests. Both the SMC1A and SMC3 gene mutation tests were negative in all. A heterozygous mutation in exon 20 of the NIPBL gene in proband 2, and a heterozygous mutation in intron 38 of the NIPBL gene in proband 3 were found in 1 patient, and RT-PCR revealed a splicing mutation in exon 38, generating both normal transcript and an aberrant alternatively spliced transcript with exon 38 deletion.ConclusionsClinical manifestations of CdLS patients from China are similar to those in the other countries. Heterozygous mutations of NIPBL gene were found.

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Section: Resultsmentioning

confidence: 99%

Clinical and genetic study of 20 patients from China with Cornelia de Lange syndrome

Hei

Gao²,

2018

BMC Pediatr

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“…Only 5 previously reported Chinese CdLS patients underwent gene analysis, and 3 cases were found to be carrying heterozygous mutations in the NIPBL gene, including c.4321G > T in exon 20, c.6589 + 5G> C in intron 38 and c.7176T > A in exon 42 (Yang, Xu, & Wang, 2017;Zhong, Liang, Liu, Xue, & Wu, 2012). The male/female ratio in the Chinese cohort of 26 individuals with CdLS was 1:1.6 (10:16).…”

Section: Genetic Analysis Findingsmentioning

confidence: 99%

A report of 2 cases of Cornelia de Lange syndrome (CdLS) and an analysis of clinical and genetic characteristics in a Chinese CdLS cohort

Miao

Yang

et al. 2019

Molec Gen & Gen Med

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Background Cornelia de Lange syndrome (CdLS) is a rare dominantly inherited developmental disorder with an estimated prevalence of 0.5–10:100,000 and no racial disparity in prevalence. The aim of this study was to present two unrelated Chinese CdLS individuals with mutations in NIPBL and to perform a comprehensive analysis of a Chinese cohort with CdLS. Subjects and methods Two unrelated Chinese patients complaining of short stature were referred to the outpatient department of Peking Union Medical College Hospital (PUMCH). Their clinical data at birth and at the most recent assessment were collected. Mutation analysis was carried out by whole exome sequencing. Twenty‐four Chinese cases with CdLS were identified through a systematic review of the literature published between 1987 and 2017. Results Two patients presented with typical phenotypes, characteristic complications of CdLS and mutations in the NIPBL gene. The average age at diagnosis of the 26 Chinese cases was higher than that of other cohorts. The frequencies of characteristic manifestations of CdLS were similar with those of other populations. Conclusions By investigating 26 Chinese cases of CdLS, we observed that the clinical data and gene variants in the Chinese cohort of CdLS patients were generally in accordance with those of other populations.

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“…In addition, Nipbl interacts with neural transcription factor Zfp609 to regulate cortical neuron migration in brain development (Van den Berg et al, 2017). A spectrum of abnormalities of the skeleton, such as microcephaly, hypophalangism, and cleft palate, are reported in CdLS patients (Barisic et al, 2008;Cheng et al, 2014;Hei et al, 2018;Krawczynska et al, 2018;Mannini et al, 2013;Selicorni et al, 2007;Zhong et al, 2012). A couple of studies mentioned that Nipbl affected craniofacial development with MAU2 (Smith et al, 2014) and interfered with limb development by dysregulation of Hox gene expression (Muto et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Defects of cohesin loader lead to bone dysplasia associated with transcriptional disturbance

Wang

et al. 2021

Journal Cellular Physiology

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Cohesin loader nipped-B-like protein (Nipbl) is increasingly recognized for its important role in development and cancer. Cornelia de Lange Syndrome (CdLS), mostly caused by heterozygous mutations of Nipbl, is an autosomal dominant disease characterized by multiorgan malformations. However, the regulatory role and underlying mechanism of Nipbl in skeletal development remain largely elusive. In this study, we constructed a Nipbl-a Cas9-knockout (KO) zebrafish, which displayed severe retardation of global growth and skeletal development. Deficiency of Nipbl remarkably compromised cell growth and survival, and osteogenic differentiation of mammalian osteoblast precursors. Furthermore, Nipbl depletion impaired the cell cycle process, and caused DNA damage accumulation and cellular senescence. In addition, nucleolar fibrillarin expression, global rRNA biogenesis, and protein translation were defective in the Nipbl-depleted osteoblast precursors. Interestingly, an integrated stress response inhibitor (ISRIB), partially rescued Nipbl depletion-induced cellular defects in proliferation and apoptosis, osteogenesis, and nucleolar function. Simultaneously, we performed transcriptome analysis of Nipbl deficiency on human neural crest cells and mouse embryonic fibroblasts in combination with Nipbl ChIP-Seq. We found that Nipbl deficiency caused thousands of differentially expressed genes including some important genes in bone and cartilage development. In conclusion, Nipbl deficiency compromised skeleton development through impairing osteoblast precursor cell proliferation and survival, and osteogenic differentiation, and also disturbing the expression of some osteogenesis-regulatory genes. Our study elucidated that Nipbl played a pivotal role in skeleton development, and supported the fact that treatment of ISRIB may provide an early intervention strategy to alleviate the bone dysplasia of CdLS.

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Mutation Analysis in Chinese Patients with Cornelia de Lange Syndrome

Cited by 4 publications

References 10 publications

Clinical and genetic study of 20 patients from China with Cornelia de Lange syndrome

Clinical and genetic study of 20 patients from China with Cornelia de Lange syndrome

A report of 2 cases of Cornelia de Lange syndrome (CdLS) and an analysis of clinical and genetic characteristics in a Chinese CdLS cohort

Defects of cohesin loader lead to bone dysplasia associated with transcriptional disturbance

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