| Autor: |
Moch, Johanna, Radtke, Maximilian, Gburek-Augustat, Janina, Karnstedt, Maike, Schönnagel, Senta, Drukewitz, Stephan H., Pilgram, Laura, Hentschel, Julia, Schumann, Isabell |
| Předmět: |
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| Zdroj: |
Frontiers in Genetics; 2024, p1-6, 6p |
| Abstrakt: |
Uniparental disomy (UPD) is the inheritance of both alleles of a chromosome from only one parent. So far, the detection of UPDs in sequencing data is not well established and a known gap in next-generation sequencing (NGS) diagnostics. By developing a new tool for UPD detection, we re-evaluated an eight-year-old individual presenting with scoliosis, muscle weakness and global developmental delay. Previous panel analysis identified a homozygous likely pathogenic loss-of- function variant in the PIEZO2-gene associated with arthrogryposis (OMIM # 617146). Interestingly, during a re-evaluation process, we identified a region of homozygosity (ROH) covering over 95% of chromosome 18. Segregation and microsatellite analysis within the family revealed that only the father is a heterozygous carrier of the variant in PIEZO2 and confirmed paternal uniparental isodisomy (iUPD) on chromosome 18 in the individual. Further methylation analysis indicated demethylation of the promotor region of PARD6G-AS1, which is described to be maternally imprinted and could possibly influence the individuals’ phenotype. Our report describes the first complete iUPD on chromosome 18 and highlights that UPDs can be a cause for homozygous pathogenic variants, which reduces the risk of reoccurrence in case of a new pregnancy in comparison to an autosomal recessive inheritance trait significantly. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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