Analysis of clinical and genetic characteristics in 10 Chinese individuals with Cornelia de Lange syndrome and literature review.
Chinese CdLS individuals
Cornelia de Lange syndrome
genotype-phenotype relationship
variant
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
03
05
2020
revised:
30
07
2020
accepted:
04
08
2020
pubmed:
29
8
2020
medline:
1
6
2021
entrez:
29
8
2020
Statut:
ppublish
Résumé
Cornelia de Lange syndrome (CdLS) is a rare congenital developmental disorder with variable multisystem involvement and genetic heterogeneity. We aimed to analyze the clinical and genetic characteristics of Chinese individuals with CdLS. We collected data regarding the neonatal period, maternal status, clinical manifestation, including facial dimorphisms and development, and follow-up treatment for individuals diagnosed with CdLS. In individuals with suspected CdLS, high-throughput sequencing, Sanger sequencing, and real-time qualitative PCR were used to verify the diagnosis. Variants, including six that were novel, were concentrated in the NIPBL (70%), HDAC8 (20%), and SMC3 (10%) genes. We found two nonsense, three splicing, and two deletion variants in NIPBL; a missense variant and an absence variant in HDAC8; and a missense variant in SMC3. Eleven cardinal features of CdLS were present in more than 80% of Chinese individuals. Compared with non-Chinese individuals of diverse ancestry, there were significant differences in the clinical characteristics of eight of these features. Six novel pathological variants were identified; thus, the study expanded the gene variant spectrum. Furthermore, most cardinal features of CdLS found in Chinese individuals were also found in individuals from other countries. However, there were significant differences in eight clinical features.
Sections du résumé
BACKGROUND
Cornelia de Lange syndrome (CdLS) is a rare congenital developmental disorder with variable multisystem involvement and genetic heterogeneity. We aimed to analyze the clinical and genetic characteristics of Chinese individuals with CdLS.
METHODS
We collected data regarding the neonatal period, maternal status, clinical manifestation, including facial dimorphisms and development, and follow-up treatment for individuals diagnosed with CdLS. In individuals with suspected CdLS, high-throughput sequencing, Sanger sequencing, and real-time qualitative PCR were used to verify the diagnosis.
RESULTS
Variants, including six that were novel, were concentrated in the NIPBL (70%), HDAC8 (20%), and SMC3 (10%) genes. We found two nonsense, three splicing, and two deletion variants in NIPBL; a missense variant and an absence variant in HDAC8; and a missense variant in SMC3. Eleven cardinal features of CdLS were present in more than 80% of Chinese individuals. Compared with non-Chinese individuals of diverse ancestry, there were significant differences in the clinical characteristics of eight of these features.
CONCLUSION
Six novel pathological variants were identified; thus, the study expanded the gene variant spectrum. Furthermore, most cardinal features of CdLS found in Chinese individuals were also found in individuals from other countries. However, there were significant differences in eight clinical features.
Identifiants
pubmed: 32856424
doi: 10.1002/mgg3.1471
pmc: PMC7549606
doi:
Substances chimiques
Cell Cycle Proteins
0
Chondroitin Sulfate Proteoglycans
0
Chromosomal Proteins, Non-Histone
0
NIPBL protein, human
0
Repressor Proteins
0
SMC3 protein, human
0
HDAC8 protein, human
EC 3.5.1.98
Histone Deacetylases
EC 3.5.1.98
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1471Informations de copyright
© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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