Background: The clinical heterogeneity of the 22q11.2 Deletion Syndrome (22q11.2DS - OMIM, #188400 and #192430) is a universal challenge leading to diagnostic delay. The aim of this study was to evaluate a low cost strategy for the diagnosis of this condition based upon clinical criteria previously reported. Health professionals, who collected clinical data, from twelve centers were trained in those criteria, which were summed through an online application (CranFlow).
Results: Clinical and laboratorial data of 347 individuals registered from 2008 to 2017 in the Brazilian Database on Craniofacial Anomalies/22q11.2 Deletion Syndrome, were reviewed. They were divided in two groups: (I) 168 individuals investigated before the definition of the criteria and (II) 179 individuals investigated after the criteria application. All of them were investigated for 22q11.2DS by Fluorescent in situ Hybridization (FISH) and/or Multiplex Ligation Probe-dependent Amplification (MLPA), detecting 98 cases with 22q11.2DS. Among the individuals with 22q11.2DS in Group II, 42/53 (79.25%) fulfilled the proposed criteria against 11/53 (20.75%) who did not fulfill them (p < .0001). The association of congenital heart diseases with high predictive value for 22q11.2DS and hypernasal voice were significantly associated to the presence of 22q11.2DS (p = 0.0172 and p < .0001, respectively). In addition, 22q11.2DS was confirmed 3.82 more times when the individuals fulfilled the proposed criteria. Of the 249 cases negative for the typical deletion in 22q11.2, Chromosomal Microarray Analysis (CMA) was performed in 132 individuals and detected pathogenic alterations at other genomic regions in 19 individuals, and variants of uncertain clinical significance in 31 cases.
Conclusions: Therefore, a locus-specific approach could be used to individuals with positive criteria as a cost-effective alternative for 22q11.2DS diagnosis. The authors discuss advantages and suggest ways of implementing this approach to investigate 22q11.2DS in a public health system.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547599 | PMC |
| http://dx.doi.org/10.1186/s13023-019-1098-1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Development and validation of a multiplex chip-based droplet digital PCR method for detecting CNVs in 7q11.2 and 22q11.2 regions.
Clin Chim Acta
December 2024
Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Diseases, Center of Laboratory Medicine, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
Copy number variations (CNVs) in the 7q11.2 and 22q11.2 chromosomal regions are major contributors to genetic disorders such as Williams-Beuren syndrome and 22q11.
View Article and Find Full Text PDFNovel Digital Anomalies, Hippocampal Atrophy, and Mutations Expand the Genotypic and Phenotypic Spectra of CNKSR2 in the Houge Type of X-Linked Syndromic Intellectual Development Disorder (MRXSHG).
Am J Med Genet A
December 2024
Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha, Qatar.
The Houge type of X-linked syndromic intellectual developmental disorder (MRXSHG) encompasses a spectrum of neurodevelopmental disorders characterized by intellectual disability (ID), language/speech delay, attention issues, and epilepsy. These conditions arise from hemizygous or heterozygous deletions, along with point mutations, affecting CNKSR2, a gene located at Xp22.12.
View Article and Find Full Text PDFA Whole MED12 Gene Deletion in a Female Fetus With Features Encountered in Hardikar Syndrome.
Prenat Diagn
December 2024
Central Lab (Genetics Lab), Longgang District Maternity & Child Healthcare Hospital of Shenzhen City (Longgang Maternity and Child Institute of Shantou University Medical College), Shenzhen, China.
Article Synopsis
- Chromosomal analysis using CMA, MS-MLPA, and trio-WES was conducted on a female fetus with omphalocele, identifying a new 300-kb deletion in the Xq13.1 region affecting the MED12 gene.
- An ultrasound at 18 weeks showed features indicative of Hardikar syndrome, such as cleft lip and palate, diaphragmatic hernia, and heart displacement.
- The findings suggest that the deletion of the MED12 gene may play a critical role in the development of Hardikar syndrome, highlighting the potential impact of haploinsufficiency of this gene.
Role of ZFHX4 in orofacial clefting based on human genetic data and zebrafish models.
Eur J Hum Genet
December 2024
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Orofacial clefting (OFC) is a frequent congenital anomaly and can occur either in the context of underlying syndromes or in isolation (nonsyndromic). The two common OFC phenotypes are cleft lip with/without cleft palate (CL/P) and cleft palate only (CPO). In this study, we searched for penetrant CL/P genes, by evaluating de novo copy number variants (CNV) from an exome sequencing dataset of 50 nonsyndromic patient-parent trios.
View Article and Find Full Text PDFOligoastrocytoma: The Vanishing Entity With True Dual Genotype, a Report, its Molecular Profiles and Review of Literature.
Int J Surg Pathol
December 2024
Department of Neurosurgery, Fortis Memorial Research Institute, Gurugram, India.
Isocitrate dehydrogenase (IDH) mutant gliomas are classified as astrocytoma or oligodendroglioma based on the recent application of mutation, mutation, and 1p/19q co-deletion. Astrocytomas classically show and mutations, whereas oligodendrogliomas are defined by 1p/19q co-deletion. However, there are reports of gliomas that harbor both astrocytoma and oligodendroglioma morphologically and molecularly.
View Article and Find Full Text PDFWant 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!