Recessive CHRM5 variant as a potential cause of neurogenic bladder.
PMID 37213061 | PMCID PMC10527291 | DOI 10.1002/ajmg.a.63241 · American journal of medical genetics. Part A · 2023
Neurogenic bladder is caused by disruption of neuronal pathways regulating bladder relaxation and contraction. In severe cases, neurogenic bladder can lead to vesicoureteral reflux, hydroureter, and chronic kidney disease. These complications overlap with manifestations of congenital anomalies of the kidney and urinary tract (CAKUT). To identify novel monogenic causes of neurogenic bladder, we applied exome sequencing (ES) to our cohort of families with CAKUT. By ES, we have identified a homozygous missense variant (p.Gln184Arg) in CHRM5 (cholinergic receptor, muscarinic, 5) in a patient with neurogenic bladder and secondary complications of CAKUT. CHRM5 codes for a seven transmembrane-spanning G-protein-coupled muscarinic acetylcholine receptor. CHRM5 is shown to be expressed in murine and human bladder walls and is reported to cause bladder overactivity in Chrm5 knockout mice. We investigated CHRM5 as a potential novel candidate gene for neurogenic bladder with secondary complications of CAKUT. CHRM5 is similar to the cholinergic bladder neuron receptor CHRNA3, which Mann et al. published as the first monogenic cause of neurogenic bladder. However, functional in vitro studies did not reveal evidence to strengthen the status as a candidate gene. Discovering additional families with CHRM5 variants could help to further assess the genes' candidate status.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | CHRM5 | “Recessive CHRM5 variant as a potential cause of neurogenic bladder.” | 0.98 | hgnc_dict_v1 |
| gene | CHRNA3 | “CHRM5 is similar to the cholinergic bladder neuron receptor CHRNA3, which Mann et al. published as the first monogenic cause of neurogenic bladder.” | 0.98 | hgnc_dict_v1 |
| phenotype | renal failure | “In severe cases, neurogenic bladder can lead to vesicoureteral reflux, hydroureter, and chronic kidney disease.” | 0.93 | phenotype_alias_lexicon_v2 |
| variant | p.Gln184Arg | “By ES, we have identified a homozygous missense variant (p.Gln184Arg) in CHRM5 (cholinergic receptor, muscarinic, 5) in a patient with neurogenic bladder and secondary complications of CAKUT.” | 0.95 | hgvs_regex_v1 |