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Catalog
2023 ACMG Annual Clinical Genetics Meeting Digital ...
3q28 Microdeletions Involving
TP63
Are As ...
3q28 Microdeletions Involving
TP63
Are Associated with Cleft Lip/Palate in a Size- and Position-Dependent Manner
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Pdf Summary
A study conducted by researchers from various institutions aimed to investigate the association between microdeletions involving the TP63 gene and cleft lip/palate (CLP). TP63-related disorders are characterized by various clinical phenotypes, including orofacial clefting, limb abnormalities, and ectodermal dysplasia. While TP63 is believed to be intolerant to loss-of-function mutations, only a few haploinsufficient alleles have been identified. Previous reports have suggested a link between microdeletions involving TP63 and CLP.<br /><br />The study included 11 patients, including a family with monozygotic twins, who had deletions involving the TP63 gene. A 498 kb deletion that included TP63 exons 2-14 and the neighboring gene P3H2 was identified in the twins, who had CLP and mild developmental delay/intellectual disability. Nine other deletions involving TP63 were also identified, including three in patients with CLP and one in a patient with unspecified congenital anomalies of the skull and face bones.<br /><br />It was observed that CLP was often associated with smaller deletion sizes (<3.2 Mb), while patients with larger deletions (>4 Mb) did not exhibit CLP. Larger deletions in patients without CLP extended into 3q27, indicating possible position-dependent effects.<br /><br />The study concluded that TP63 microdeletions are indeed associated with CLP, but there is variability in the clinical features among individuals with these deletions, suggesting incomplete penetrance and variable expressivity. The study also suggested that there may be genotype-phenotype correlations associated with TP63 haploinsufficiency, but further research is needed to understand the mechanisms behind the size- and position-dependent differences in clinical phenotypes.<br /><br />Overall, this study provides further evidence of the association between TP63 microdeletions and CLP, but also highlights the need for more research to better understand the genetic interactions and mechanisms underlying these deletions' effects on clinical variation.
Asset Subtitle
Presenting Author - Daniel P. Reich, PhD; Co-Author - Amanda S. Openshaw, MS, CGC; Co-Author - Michele Garcia, MS, LCGC; Co-Author - Inder Gadi, PhD, FACMG; Co-Author - Madelena Martin, MD; Co-Author - Hiba Risheg; Co-Author - Bo Hong, MD, FACMG;
Meta Tag
Clinical Applications of Molecular Cytogenetics
Congenital Anomaly
Genetic Testing
Genotype-Phenotype Correlations
Malformation
Microarray
Co-Author
Amanda S. Openshaw, MS, CGC
Co-Author
Michele Garcia, MS, LCGC
Co-Author
Inder Gadi, PhD, FACMG
Co-Author
Madelena Martin, MD
Co-Author
Hiba Risheg
Co-Author
Bo Hong, MD, FACMG
Presenting Author
Daniel P. Reich, PhD
Keywords
microdeletions
TP63 gene
cleft lip/palate
TP63-related disorders
limb abnormalities
ectodermal dysplasia
haploinsufficient alleles
monozygotic twins
deletion sizes
genotype-phenotype correlations
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