Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3.
Suzanne Hosie, Melina Ellis, Mathusi Swaminathan and 16 others
PMID 31119867WHAT IT FOUND
Two brothers with an autism-associated neuroligin-3 mutation had diarrhea, regurgitation, and gut pain.
Mice carrying the same mutation had faster small-intestinal transit and altered colon movement when gut nerve signals were blocked.
Key findings
01The two autism siblings carrying the R451C mutation had gastrointestinal symptoms: the older brother had diarrhea, fecal incontinence, post-meal regurgitation and esophageal inflammation; the younger brother had diarrhea, chronic intestinal pain and significantly delayed bladder and bowel control.
02Mice carrying the R451C mutation had faster small intestinal transit than wild-type mice, with dye front to small intestine length ratios of 0.46 ± 0.03 in wild-type mice and 0.58 ± 0.04 in mutant mice.
03When GABA A receptor blockers bicuculline or gabazine were applied to isolated mutant mouse colon, movement was reduced compared with wild-type colon; the GABA B blocker CGP 54626 did not change movement.
STILL TO COME
How it was doneWhat they found
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What it does not show
The human evidence was only two brothers' case notes, so it cannot show that the mutation causes gastrointestinal symptoms in autism. No occupational therapy or other treatment was tested in patients. The mouse colon experiments used tissue isolated from the brain and circulating hormones, so they do not show what happens in a living person. No power analysis was available for colon motor counts. A genotype by drug interaction could not be tested because enough experiments were not ethically feasible. No correction for multiple comparisons was used for colon motor frequency analyses. The study examined a rare mutation, not autism as a whole.
Declared interests
The authors declared no conflict of interest. The supplied publication types list NIH, non-U.S. government, and U.S. government non-P.H.S. research support.
The easy way to misread this
Do not read this as proof that the R451C mutation causes gastrointestinal symptoms in all people with autism. Do not read the GABA blocker findings as a treatment plan for patients. The human part was two case notes, and the drug findings were in isolated mouse colon.