AI Article Synopsis

  • Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder marked by a variety of symptoms including growth delays, upper limb issues, and other systemic problems, primarily caused by mutations in specific genes associated with the cohesin complex.
  • The majority of CdLS cases (over 60%) are linked to mutations in the NIPBL gene, which leads to the most severe form of the syndrome; other cohesin gene mutations typically result in milder symptoms.
  • The study analyzed the genetic factors in 716 individuals with CdLS to better understand the contributions of cohesin complex genes and identify potential new candidate genes, improving knowledge of genetic variations and their effects on CdLS manifestations.

Article Abstract

Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (>60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS-like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or "DTRs"). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype-phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10524367PMC
http://dx.doi.org/10.1002/ajmg.a.63247DOI Listing

Publication Analysis

Top Keywords

cornelia lange
8
lange syndrome
8
novel candidate
8
genes
8
candidate genes
8
genes genotype-phenotype
8
genotype-phenotype correlations
8
pathogenic variants
8
variants genes
8
genes encoding
8

Similar Publications

Around 15% of children and adolescents in Germany are overweight or obese. To support the planning, implementation and evaluation of preventive activities, the Robert Koch Institute (RKI) has developed a population-wide monitoring of influencing factors relevant to the development of obesity during childhood (AdiMon). AdiMon is a web-based indicator system providing population-wide meaningful and regularly updated data on factors that influence obesity in kindergarten-age girls and boys (0- to 6-years-old).

View Article and Find Full Text PDF
Article Synopsis
  • The study aims to analyze risky alcohol consumption (RAC) and heavy episodic drinking (HED) among parents in Germany, focusing on its prevalence and associations with sociodemographic factors.
  • Data from nationwide surveys (2009-2012) included responses from over 16,000 parents, gathering information on their alcohol consumption habits using the AUDIT-C screening tool.
  • Findings revealed significant percentages of parents engaged in RAC and HED, with associations found between these drinking patterns and variables like education, income, and relationship status, highlighting the need for targeted preventive measures to support child development.
View Article and Find Full Text PDF

The scientific assessment of health issues, the design and further development of political guidelines as well as the targeted planning of measures in the European Union (EU) require data on population health. For this reason, all EU Member States regularly collect data on the health status, provision of healthcare, health determinants and socioeconomic situation of their respective populations in the European Health Interview Survey (EHIS). Participants are at least 15 years old and live in private households.

View Article and Find Full Text PDF
Article Synopsis
  • The study examined the trends in healthy lifestyle prevalence in Germany from 1990 to 2011, analyzing data from over 18,000 adults aged 25-69 across three national health surveys.
  • The overall prevalence of individuals meeting at least four out of five healthy behaviors increased significantly, from 9.3% in 1990-92 to 14.7% in 2008-11, reflecting a 58.1% relative change.
  • While both men and women showed increases in healthy lifestyles, the disparity in prevalence between genders grew, and higher educated groups experienced the most significant improvements, while low and medium educated groups showed little change.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!