Novel <i>KMT5B</i> variant associated with neurodevelopmental disorder in a Chinese family: A case report.
Consider KMT5B testing when autism, intellectual disability, and motor clumsy features travel together.
01Research in Context
What this study did
Tong et al. (2024) wrote about two brothers in one Chinese family.
Both boys have autism, intellectual disability, and delayed milestones.
The team found a brand-new KMT5B gene change shared by the brothers.
What they found
The KMT5B variant is labeled "likely pathogenic."
The boys also show low muscle tone and subtle facial differences.
No treatment results are given; the paper is a pure description.
How this fits with other research
Johnson et al. (2021) first showed that mice missing one Kmt5b copy act autistic.
Their mouse data gives the Tong case a ready-made biology story.
Mazzone et al. (2012) saw autism fade over time in two kids with a 2q37 deletion.
That fading looks different from the steady picture Tong reports, but the genes sit in similar chromatin-control pathways, so the contrast may help us learn why some kids improve while others do not.
Why it matters
If you assess a child with ASD plus low tone, clumsy gait, and a long face, add KMT5B to your genetic referral list. Knowing the exact change can end the diagnostic hunt and guide family planning. Track motor skills closely; the mouse work hints they may need extra PT and adaptive PE.
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02At a glance
03Original abstract
We report here the clinical and genetic features of KMT5B-related neurodevelopmental disorder caused by a novel heterozygous frameshift variant in KMT5B in a Chinese family. A 7-year-old Chinese boy with mild-to-moderate intellectual disability, significant language impairment, motor disability, and coordination difficulties presented to our hospital because he “could not speak and did not look at others.” He was diagnosed with autism spectrum disorder previously owing to developmental delays in cognition, language expression, and understanding. The child also had variable nonspecific features including macrocephaly, wide button-hole space and nasal bridge, low ear, social behavior disorder, and foot deformities. Exome sequencing (ES) revealed that both the proband and his younger brother had inherited a novel heterozygous frameshift variant c.438_439ins[ASD; KT192064.1:1_310] of the KMT5B gene from their father. Bioinformatics analysis showed that the novel mutation affected the structure of the KMT5B pre-SET domain, mainly in the α-helix region. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, this type of variant was eventually determined to be likely pathogenic (PVS1+PM2_P). Our investigation expands the mutation spectrum of KMT5B to help us to better understand KMT5B-related neurodevelopmental disorder.
Heliyon, 2024 · doi:10.1016/j.heliyon.2024.e28686