A deletion involving CD38 and BST1 results in a fusion transcript in a patient with autism and asthma.
A rare BST1-CD38 fusion from a 4p deletion may link immune problems to autism regression.
01Research in Context
What this study did
Doctors studied two sisters with autism. Both lost words after age two. Only the younger girl had a tiny missing piece on chromosome 4.
The missing DNA fused two genes, BST1 and CD38, into one new message. The team checked if this fusion could worsen autism or asthma.
What they found
The fusion transcript was found only in the sister who lost speech and later got asthma. Her older sister, without the deletion, kept more words.
Because the mother carried the same deletion but had no autism, the fusion may act as a risk dial, not a switch.
How this fits with other research
Mount et al. (2011) tracked the families and saw speech loss in 1 of every the kids with autism. Most families did not show a clear genetic link, so a single rare deletion like this one is an outlier.
Eisenhower et al. (2006) found kids who regress are twice as likely to have relatives with autoimmune thyroid disease. The sisters in this study also have asthma, another immune problem. The new fusion could sit in the same immune pathway.
Nader-Grosbois et al. (2012) reported a different small deletion on chromosome 16 that caused autism in one girl. Together, these case studies build a pattern: tiny chromosome glitches can tip the scale when other risks are present.
Why it matters
You may never see this exact 4p deletion again, but the story teaches two things. First, ask about immune issues in the family when a child with autism loses skills. Second, if you see both regression and asthma, consider a genetics consult. The fusion may open new paths for immune-targeted supports.
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02At a glance
03Original abstract
CD38 encodes a ligand in the oxytocin signaling pathway. Some single nucleotide polymorphisms in this gene have been associated with low serum oxytocin levels in autism spectrum disorder (ASD) patients. Oxytocin disruption has been hypothesized to account for features of ASD, including impaired communication and social behavior, based on animal studies. Recent human studies have shown administration of oxytocin improving emotion recognition, promoting social behavior, and improving auditory processing of social stimuli in ASD patients. In addition to its role in oxytocin signaling, CD38 is involved in the regulation of calcium concentration in airway smooth muscle with impairment of CD38 being implicated in airway diseases like asthma. While a number of studies have implicated rare chromosomal deletions and duplications in helping determine genetic risk for autism, there are to our knowledge no reports describing rearrangements involving CD38 or deletions in patients with ASD. Here, we present two sisters diagnosed with autism and with features of regression-previously acquired speech lost in the second year of life. The younger sister, who also had asthma, inherited a maternal deletion of 4p15.32 that results in a BST1-CD38 fusion transcript. Their mother's deletion was mosaic and she was not affected. Although further work is required to assess functional consequences of the fusion transcript, we hypothesize that the proband's deletion may have served as a risk factor for autism that, when combined with other susceptibility variants, resulted in a more severe presentation than her sister.
Autism research : official journal of the International Society for Autism Research, 2014 · doi:10.1002/aur.1365