TY - JOUR
T1 - Recessive Dystrophic Epidermolysis bullosa due to Hemizygous 40 kb Deletion of COL7A1 and the Proximate PFKFB4 Gene Focusing on the Mutation c.425A>G Mimicking Homozygous Status
AU - Klausegger, Alfred
AU - Jeschko, Niklas
AU - Grammer, Markus
AU - Cemper-Kiesslich, Jan
AU - Neuhuber, Franz
AU - Diem, Anja
AU - Breitenbach-Koller, Hannelore
AU - Sander, Gabriele
AU - Kotzot, Dieter
AU - Bauer, Johann Wolfgang
AU - Laimer, Martin
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/10/11
Y1 - 2022/10/11
N2 - Background: Dystrophic Epidermolysis bullosa (DEB) is a rare inherited mechanobullous disease characterised by the hyperfragility of the skin and mucous membranes. It is (typically) caused by (loss-of-function) mutations in the COL7A1 gene that impair the formation of collagen type VII, which represents the major constituent of anchoring fibrils within the basement membrane zone of epithelialised tissues. In a 4-year-old patient diagnosed with the clinical features of recessive DEB, genotyping via Next-Generation EB Panel Sequencing initially revealed the homozygosity of the maternal c.425A>G mutation, while the paternal heterozygosity in exon 3 was lacking. This genetic profile suggested incongruent gene transmission due to uniparental isodisomy (UPD) or the occurrence of a hemizygous deletion of unknown size. Methods: Thus, the EB panel sequencing of genomic DNA, followed by a paternity test and analysis of microsatellite markers, as well as multiplex ligation-dependent probe amplification (MLPA) copy number analysis using patient and parental DNA, were performed. Results: This approach revealed a paternally derived hemizygous deletion spanning from exon 3 to exon 118. Linear amplification-mediated PCR (LAM-PCR) determined the breaking points within intron 2 of the COL7A1 gene, comprising a 40kb segment within intron 1 of the adjacent PFKFB4 gene. Conclusion: This report highlights the relevance of advanced molecular profiling to determine new/exceptional/unusual genotypes and the accurate mode of genetic transmission in DEB.
AB - Background: Dystrophic Epidermolysis bullosa (DEB) is a rare inherited mechanobullous disease characterised by the hyperfragility of the skin and mucous membranes. It is (typically) caused by (loss-of-function) mutations in the COL7A1 gene that impair the formation of collagen type VII, which represents the major constituent of anchoring fibrils within the basement membrane zone of epithelialised tissues. In a 4-year-old patient diagnosed with the clinical features of recessive DEB, genotyping via Next-Generation EB Panel Sequencing initially revealed the homozygosity of the maternal c.425A>G mutation, while the paternal heterozygosity in exon 3 was lacking. This genetic profile suggested incongruent gene transmission due to uniparental isodisomy (UPD) or the occurrence of a hemizygous deletion of unknown size. Methods: Thus, the EB panel sequencing of genomic DNA, followed by a paternity test and analysis of microsatellite markers, as well as multiplex ligation-dependent probe amplification (MLPA) copy number analysis using patient and parental DNA, were performed. Results: This approach revealed a paternally derived hemizygous deletion spanning from exon 3 to exon 118. Linear amplification-mediated PCR (LAM-PCR) determined the breaking points within intron 2 of the COL7A1 gene, comprising a 40kb segment within intron 1 of the adjacent PFKFB4 gene. Conclusion: This report highlights the relevance of advanced molecular profiling to determine new/exceptional/unusual genotypes and the accurate mode of genetic transmission in DEB.
KW - Epidermolysis bullosa
KW - RDEB
KW - deletion
KW - COL7A1
KW - hemizygosity
KW - MLPA
KW - LAM-PCR
KW - COL7A1
KW - Epidermolysis bullosa
KW - LAM-PCR
KW - MLPA
KW - RDEB
KW - deletion
KW - hemizygosity
UR - http://www.scopus.com/inward/record.url?scp=85140623521&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/5bceb0c4-2b88-3091-b2e8-59f307746f50/
U2 - 10.3390/diagnostics12102460
DO - 10.3390/diagnostics12102460
M3 - Article
C2 - 36292148
SN - 2075-4418
VL - 12
SP - 1
EP - 14
JO - Diagnostics
JF - Diagnostics
IS - 10
M1 - 2460
ER -