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Further support linking the 22q11.2 microduplication to an increased risk of bladder exstrophy and highlighting LZTR1 as a candidate gene
- Source :
- Molecular Genetics & Genomic Medicine, Vol 7, Iss 6, Pp n/a-n/a (2019), Molecular Genetics & Genomic Medicine
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Background The bladder exstrophy‐epispadias complex (BEEC) is a congenital malformation of the bladder and urethra. The underlying causes of this malformation are still largely unknown; however, aside from environment, genetics is thought to play an essential role. The recurrent 22q11.2 microduplication is the most persistently detected genetic aberration found in BEEC cases. Methods We performed array comparative genomic hybridization (array‐CGH) analysis of 76 Swedish BEEC patients. Statistical analysis was performed on current dataset pooled with previously published data on the 22q11.2 microduplication in BEEC patients. We performed massive parallel sequencing (MPS) of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication followed by functional studies. Results We identified three additional cases with the 22q11.2 microduplication. Pooling data from this study with previously published reports showed a statistically significant enrichment of the 22q11.2 microduplication in BEEC patients (2.61% in cases vs. 0.08% in controls; OR = 32.6; p = 8.7 × 10−4). MPS of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication identified a novel variant in LZTR1 (p.Ser698Phe) in one patient. Functional evaluation of the LZTR1 p.Ser698Phe variant in live NIH 3T3 cells showed that the concentration and cytoplasmic mobility differ between the Lztr1wt and Lztr1mut, indicating a potential functional effect of the LZTR1mut. Conclusion Our study further emphasizes the involvement of the 22q11.2 region in BEEC development and highlights LZTR1 as a candidate gene underlying the urogenital malformation.
- Subjects :
- Male
0301 basic medicine
Candidate gene
Pathology
Chromosomes, Human, Pair 22
030105 genetics & heredity
confocal microscopy
urologic and male genital diseases
Mice
Risk Factors
Chromosome Duplication
Genetics (clinical)
Exome sequencing
Comparative Genomic Hybridization
female genital diseases and pregnancy complications
medicine.anatomical_structure
Chromosome Structures
array‐CGH
Medical genetics
Original Article
Female
Medical Genetics
Adult
medicine.medical_specialty
Epispadias
lcsh:QH426-470
Fluorescence spectrometry
fluorescence spectrometry
03 medical and health sciences
DiGeorge Syndrome
Genetics
medicine
Animals
Humans
Abnormalities, Multiple
Molecular Biology
Medicinsk genetik
Sweden
business.industry
microduplication
Original Articles
medicine.disease
Bladder exstrophy
lcsh:Genetics
030104 developmental biology
Increased risk
Urethra
array-CGH
NIH 3T3 Cells
LZTR1
business
bladder exstrophy
exome sequencing
Transcription Factors
Subjects
Details
- ISSN :
- 23249269
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Molecular Genetics & Genomic Medicine
- Accession number :
- edsair.doi.dedup.....405979108ee1ea751ad900afaa716380