Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Pediatrics
Published in: BMC Pediatrics 1/2018

Open Access 01-12-2018 | Research article

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

Authors: Mingyan Hei, Xiangyu Gao, Lingqian Wu

Published in: BMC Pediatrics | Issue 1/2018

Login to get access

Abstract

Background

Cornelia 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.

Methods

This 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.

Results

Twenty 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.

Conclusions

Clinical manifestations of CdLS patients from China are similar to those in the other countries. Heterozygous mutations of NIPBL gene were found.
Literature
1.
Liu J, Baynam G. Cornelia de Lange syndrome. Adv Exp Med Biol. 2010;685:111–23.PubMed
2.
Barisic I, Tokic V, Loane M, Bianchi F, Calzolari E, Garne E, et al. Descriptive epidemiology of Cornelia de Lange syndrome in Europe. Am J Genet A. 2008;146(A):51–9.CrossRef
3.
Kline AD, Krantz ID, Sommer A, Kliewer M, Jackson LG, DR FP, Levin AV, et al. Cornelia de Lange syndrome: clinical review, diagnostic and scoring systems, and anticipatory guidance. Am J Med Genet A. 2007;143A:1287–96.CrossRefPubMed
4.
Schrier SA, Sherer I, Deardorff MA, Clark D, Audette L, Gillis L, et al. Causes of death and autopsy findings in a large study cohort of individuals with Cornelia de Lange syndrome and review of the literature. Am J Med Genet A. 2011;155A:3007–24.CrossRefPubMed
5.
Wygnanski-Jaffe T, Shin J, Perruzza E, Abdolell M, Jackson LG, Levin AV. Ophthalmologic findings in the Cornelia de Lange syndrome. J AAPOS. 2005;9:407–15.CrossRefPubMed
6.
Schoumans J, Wincent J, Barbaro M, Djureinovic T, Maguire P, Forsberg L, et al. Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients. Eur J Hum Genet. 2007;15:143–9.CrossRefPubMed
7.
Kalal GI, Raina VP, Nayak VS, Teotia P, Gupta BV. Cornelia de Lange syndrome: a case study. Genet Test Mol Biomarkers. 2009;13:15–8.CrossRefPubMed
8.
Hayashi S, Ono M, Makita Y, Imoto I, Mizutani S, Inazawa J. Fortuitous detection of a submicroscopic deletion at 1q25 in a girl with Cornelia-de Lange syndrome carrying t(5;13)(p13.1;q12.1) by array-based comparative genomic hybridization. Am J Med Genet A. 2007;143A:1191–7.CrossRefPubMed
9.
Kline AD, Grados M, Sponseller P, Levy HP, Blagowidow N, Schoedel C, et al. Natural history of aging in Cornelia de Lange syndrome. Am J Med Genet C Semin Med Genet. 2007;145C:248–60.CrossRefPubMedPubMedCentral
10.
Zhong Q, Liang D, Liu J, Xue J, Wu L. Mutation analysis in Chinese patients with Cornelia de Lange syndrome. Genet Test Mol Biomarkers. 2012;16(9):1130–4.CrossRefPubMedPubMedCentral
11.
Russell KL, Ming JE, Patel K, Jukofsky L, Magnusson M, Krantz ID. Dominant paternal transmission of Cornelia de Lange syndrome: a new case and review of 25 previously reported familial recurrences. Am J Med Genet. 2001;104:267–76.CrossRefPubMedPubMedCentral
12.
Ireland M, Donnai D, Brachmann BJ. De Lange syndrome delineation of the clinical phenotype. Am J Med Genet. 1993;47:959–64.CrossRefPubMed
13.
Arbuzova S, Nikolenko M, Krantz D, Hallahan T, Macri J. Low first-trimester pregnancy-associated plasma protein-a and Cornelia de Lange syndrome. Prenat Diagn. 2003;23:864.CrossRefPubMed
14.
Aitken DA, Ireland M, Berry E, Crossley JA, Macri JN, Burn J, et al. Second-trimester pregnancy associated plasma protein-a levels are reduced in Cornelia de Lange syndrome pregnancies. Prenat Diagn. 1999;19:706–10.CrossRefPubMed
15.
Dorsett D, Krantz ID. On the molecular etiology of Cornelia de Lange syndrome. The year in human and medical genetics 2009. Ann N Y Acad Sci. 2009;1151:22–37.CrossRefPubMedPubMedCentral
16.
Krantz ID, McCallum J, DeScipio C, Kaur M, Gillis LA, Yaeger D, et al. Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila Melanogaster nipped-B. Nat Genet. 2004;36:631–5.CrossRefPubMedPubMedCentral
17.
Musio A, Selicorni A, Focarelli ML, Gervasini C, Milani D, Russo S, et al. X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations. Nat Genet. 2006;38:528–30.CrossRefPubMed
18.
Deardorff MA, Kaur M, Yaeger D, Rampuria A, Korolev S, Pie J, et al. Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation. Am J Hum Genet. 2007;80:485–94.CrossRefPubMedPubMedCentral
19.
Parenti I, Gervasini C, Pozojevic J, Wendt KS, Watrin E, Azzollini J, et al. Expanding the clinical spectrum of the 'HDAC8-phenotype' - implications for molecular diagnostics, counseling and risk prediction. Clin Genet. 2016;89:564–73.CrossRefPubMed
20.
Baynam G, Goldblatt J, Walpole I. Deletion of 8p23.1 with features of Cornelia de Lange syndrome and congenital diaphragmatic hernia and a review of deletions of 8p23.1 to 8pter a further locus for Cornelia de Lange syndrome. Am J Med Genet Part A. 2008;146A:1565–70.CrossRefPubMed
Metadata
Title
Clinical and genetic study of 20 patients from China with Cornelia de Lange syndrome
Authors
Mingyan Hei
Xiangyu Gao
Lingqian Wu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2018
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-018-1004-3

Other articles of this Issue 1/2018

BMC Pediatrics 1/2018 Go to the issue

Correction

Correction to: decision-making at the limit of viability: differing perceptions and opinions between neonatal physicians and nurses

Research article

Exclusive breastfeeding practice during first six months of an infant’s life in Bangladesh: a country based cross-sectional study

Research article

Clinical evaluation of severe neonatal Hyperbilirubinaemia in a resource-limited setting: a 4-year longitudinal study in south-East Nigeria

Research article

The association of malaria morbidity with linear growth, hemoglobin, iron status, and development in young Malawian children: a prospective cohort study

Study protocol

Does red blood cell irradiation and/or anemia trigger intestinal injury in premature infants with birth weight ≤ 1250 g? An observational birth cohort study

Research article

NRG1 variant effects in patients with Hirschsprung disease