Journal article
Exome sequencing of child–parent trios with bladder exstrophy: Findings in 26 children
American journal of medical genetics. Part A, Vol.185(10), pp.3028-3041
10/2021
DOI: 10.1002/ajmg.a.62439
PMCID: PMC8446314
PMID: 34355505
Abstract
Bladder exstrophy (BE) is a rare, lower ventral midline defect with the bladder and part of the urethra exposed. The etiology of BE is unknown but thought to be influenced by genetic variation with more recent studies suggesting a role for rare variants. As such, we conducted paired‐end exome sequencing in 26 child/mother/father trios. Three children had rare (allele frequency ≤ 0.0001 in several public databases) inherited variants in TSPAN4, one with a loss‐of‐function variant and two with missense variants. Two children had loss‐of‐function variants in TUBE1. Four children had rare missense or nonsense variants (one per child) in WNT3, CRKL, MYH9, or LZTR1, genes previously associated with BE. We detected 17 de novo missense variants in 13 children and three de novo loss‐of‐function variants (AKR1C2, PRRX1, PPM1D) in three children (one per child). We also detected rare compound heterozygous loss‐of‐function variants in PLCH2 and CLEC4M and rare inherited missense or loss‐of‐function variants in additional genes applying autosomal recessive (three genes) and X‐linked recessive inheritance models (13 genes). Variants in two genes identified may implicate disruption in cell migration (TUBE1) and adhesion (TSPAN4) processes, mechanisms proposed for BE, and provide additional evidence for rare variants in the development of this defect.
Details
- Title: Subtitle
- Exome sequencing of child–parent trios with bladder exstrophy: Findings in 26 children
- Creators
- Georgia Pitsava - Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthJohn Lane - University of Minnesota Medical SchoolDenise M Kay - Wadsworth Center, New York State Department of HealthKristin M Conway - College of Public Health, The University of IowaGary M Shaw - Stanford University School of MedicineJennita Reefhuis - National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and PreventionMary M Jenkins - National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and PreventionLynn M Almli - National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and PreventionAndrew F Olshan - Gillings School of Global Public HealthFaith Pangilinan - National Human Genome Research InstituteLawrence C Brody - National Human Genome Research InstituteRobert J Sicko - Wadsworth Center, New York State Department of HealthCharlotte A Hobbs - Rady Children's Institute for Genomic MedicineMike Bamshad - University of WashingtonDaniel McGoldrick - University of WashingtonDeborah A Nickerson - University of WashingtonRichard H Finnell - Center for Precision Environmental Health, Baylor College of MedicineJames Mullikin - National Human Genome Research Institute, National Institutes of HealthPaul A Romitti - College of Public Health, The University of IowaJames L Mills - Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of HealthUniversity of Washington Center for Mendelian GenomicsNISC Comparative Sequencing ProgramNational Birth Defects Prevention Study
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part A, Vol.185(10), pp.3028-3041
- DOI
- 10.1002/ajmg.a.62439
- PMID
- 34355505
- PMCID
- PMC8446314
- NLM abbreviation
- Am J Med Genet A
- ISSN
- 1552-4825
- eISSN
- 1552-4833
- Publisher
- John Wiley & Sons, Inc
- Number of pages
- 14
- Grant note
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HHSN27500005; HHSN275201100001I) National Human Genome Research Institute (HG006493; HG008956) Centers for Disease Control and Prevention (U01 DD001035; U01 DD001223) Division of Intramural Research of the National Human Genome Research Institute, National Institutes of Health
- Language
- English
- Date published
- 10/2021
- Academic Unit
- Epidemiology; Biostatistics
- Record Identifier
- 9984214665602771
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