A familial heterozygous null mutation of MET in autism spectrum disorder.
A super-rare MET gene deletion can cause autism plus speech and social struggles in one family, proving again that ASD has many roots.
01Research in Context
What this study did
Doctors looked at two brothers who both have autism.
They read every letter of the boys’ DNA and found a rare glitch.
The glitch knocks out a gene called MET, which helps brain cells grow.
What they found
Both brothers carry the same broken MET gene.
They also share severe language and social delays.
The parents, who have milder traits, carry the glitch too.
How this fits with other research
Mouridsen et al. (2008) and Hwang et al. (2019) show Danish and Australian adults with autism die about twice as often as others.
Those big numbers feel grim, but they count thousands of people with many causes.
The MET case gives one clear genetic straw that can bend the camel’s back.
Uljarević et al. (2017) urge us to measure sensory issues one by one instead of yes-or-no.
That call for finer detail matches this paper’s message: autism is a mixed bag, and genes like MET are one color in the pile.
Why it matters
You may never meet a child with a MET mutation, but the story reminds you that “autism” is many roads.
When progress stalls or medical issues pile up, think genetics and refer for testing.
It also softens blame—some hard behaviors ride on biology, not bad teaching.
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02At a glance
03Original abstract
Autism spectrum disorder (ASD) results from interactions of genetic and environmental factors. The MET proto-oncogene has been identified as a candidate gene for autism susceptibility, and is implicated in neurodevelopment and social brain circuitry. Here, we describe the first case of a familial mutation of MET, consisting of an interstitial genomic deletion removing exons 12 through 15, causing a frameshift and premature stop codon, with evidence of nonsense-mediated mRNA decay. On the other allele, patients carried the C allele of the MET promoter rs1858830 polymorphism, known to decrease MET expression and previously associated with autism susceptibility. The heterozygous mutation was associated with autism in one patient, and language and social impairment in a sibling. Our observations delineate the phenotypic spectrum associated with a clearly defined, very likely complete loss of function mutation of MET. Incomplete penetrance in this family was consistent with MET as a partial susceptibility gene for ASD. Implication of MET in normal and pathological brain development opens new perspectives for understanding the pathophysiology of autism and for eventual therapeutical clues.
Autism research : official journal of the International Society for Autism Research, 2014 · doi:10.1002/aur.1396