Abstract
Urinary bladder malformations associated with bladder outlet obstruction are a frequent cause of progressive renal failure in children. We here describe a muscarinic acetylcholine receptor M3 (CHRM3) (1q41-q44) homozygous frameshift mutation in familial congenital bladder malformation associated with a prune-belly-like syndrome, defining an isolated gene defect underlying this sometimes devastating disease. CHRM3 encodes the M3 muscarinic acetylcholine receptor, which we show is present in developing renal epithelia and bladder muscle. These observations may imply that M3 has a role beyond its known contribution to detrusor contractions. This Mendelian disease caused by a muscarinic acetylcholine receptor mutation strikingly phenocopies Chrm3 null mutant mice.
Highlights
Urinary bladder malformations associated with bladder outlet obstruction are a frequent cause of progressive renal failure in children
Lower urinary tract and/or kidney malformations account for 40% of childhood end-stage renal failure.[1]
A fifth affected male sibling had died soon after birth as a result of renal failure and urosepsis (II-1). He and one affected surviving brother (II-4) displayed marked abdominal wall distension and were assigned as having PBS, whereas their three brothers were considered to have ‘‘posterior urethral valves (PUVs)’’ because cystopscopy noted urethral valve-like structures
Summary
Urinary bladder malformations associated with bladder outlet obstruction are a frequent cause of progressive renal failure in children. CHRM3 (MIM 118494) encodes the M3 subtype of muscarinic acetylcholine (ACh) receptors, the major receptor mediating urinary bladder contraction upon micturition.[7] We restudied a family reported in 20055 when there were four surviving boys with congenital BOO born to consanguineous Turkish parents.
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