A Patient with a Small Deletion Affecting Only Exon 1-Intron 1 of the NXF5 Gene: Potential Evidence Supporting Its Role in Neurodevelopmental Disorders
Tiny NXF5 deletions on the X chromosome can cause autism plus severe ID in boys.
01Research in Context
What this study did
Doctors looked at one boy with autism and severe intellectual disability. They ran high-resolution DNA tests and found a tiny missing piece on his X chromosome. The deletion hits only the first bit of a gene called NXF5.
No one had ever seen this exact change before. The team compared his features with four older cases that had bigger X-chromosome losses covering the same area.
What they found
The boy’s deletion is the smallest reported so far, yet his symptoms are just as strong. He has no speech, hand-flapping, and head-banging by age four.
Because the gene sits on the X and only males were affected in all five cases, the pattern fits X-linked inheritance. This tips NXF5 as a new autism-risk gene.
How this fits with other research
Allen-Brady et al. (2010) first flagged this exact chunk of the X chromosome in a large family study. Their linkage peak pointed here; YY et al. now hand us the single-gene culprit inside that peak.
Hong et al. (2021) showed micro-arrays find an answer in about a large share of kids with unexplained ID. The new case is one more win for that same test.
Cohen et al. (2005) urged routine genetic screening for kids who look "idiopathic." This paper gives clinicians one more rare but real item to add to their checklist.
Why it matters
If you assess boys with both autism and unexplained ID, keep X-linked genes on your radar. A simple chromosomal micro-array can now pick up NXF5 deletions. When the test is positive, you can give families a clear genetic reason, steer them toward X-linked counseling, and watch for the self-injury seen in all reported cases so far.
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02At a glance
03Original abstract
Genetic studies have identified numerous candidate genes for neurodevelopmental disorders associated with intellectual disability (ID) and autism spectrum disorders (ASD). Some genetic anomalies are very rare or challenging to detect, making it essential to validate the presence of gene mutations or copy number variations in additional patients with similar clinical phenotypes. <b>Background/Objectives</b>: Case reports play a crucial role in this process by validating rare variants in phenotypically matched patients, shedding light on novel candidate genes linked to these disorders. <b>Methods</b>: Patients with ID and ASD underwent neurological examinations, brain magnetic resonance imaging (MRI), sleep and wake electroencephalogram (EEG), neuropsychological evaluations, and laboratory tests including molecular analysis for fragile-X syndrome and array comparative genomic hybridization (aCGH). <b>Results</b>: We observed a patient with ID and ASD who carried a microdeletion in Xq22.1 that affects only exon 1 and intron 1 of the Nuclear RNA Export Factor 5 (<i>NXF5</i>) gene. The patient's phenotypic features overlap with those of the only four previously reported cases of variations involving the same gene. <b>Conclusions</b>: Our findings suggest that <i>NXF5</i> may play a role in neurodevelopmental disorders and should be considered in the spectrum of X-linked ID associated with ASD.
, 2025 · doi:10.3390/genes16050571