Our research
Our case series.
Our ongoing research characterizes one of the more detailed UPF3B pedigree series described to date, built from our own extended family and families connected through it.
13
Affected males identified to date
3
Confirmed by genetic testing
5
Pedigrees in our case series
2026
Accepted for poster presentation at ASHG
Of the 13 affected males identified, 3 have molecular confirmation by genetic testing and the remainder are clinically diagnosed. Multiple carrier females have also been identified, some confirmed by genetic testing and others inferred from their position on the pedigree. The pedigrees span an extended family of roughly 75 to 80 relatives. The oldest affected member known to us is 80 years old. These counts are current as of the date below and will be updated as testing continues.
How this series came together.
Most published rare-disease case series begin in a clinic. This one began at a kitchen table, with a family that had been told for decades there was no explanation to find.
1. Gathering the historyPhone calls with relatives across several cities, collecting medical histories, ages, and outcomes for affected and unaffected members reaching back five generations.
2. Building the pedigreeTurning those interviews into formal pedigree charts using genetic pedigree software, until the inheritance pattern became visible for the first time.
3. Narrowing the causeReviewing published case reports and clinical literature on X-linked intellectual disability to shortlist the conditions that could produce this pattern.
4. Confirming itWorking with genetics specialists and a diagnostic laboratory to arrange whole exome sequencing, which identified a rare frameshift variant in UPF3B.
Decades of individual clinical visits had produced no diagnosis. What finally worked was assembling the whole family at once, rather than examining one affected person at a time.
Where this stands.
ASHG 2026. This work will be presented as a poster at the American Society of Human Genetics annual meeting in October 2026.
Manuscript. Currently in preparation for submission to a peer-reviewed genetics journal. Authors: Vidushi Gupta (first and corresponding) and Anirudh Gupta.
Access to testing. Through a laboratory collaboration, we secured a 70 percent discount on genetic testing, saving participating families roughly INR 100,000 to date. The collaborating laboratory will be named here once that partnership is formalized.
Data and privacy. All figures shown here are aggregate. No individually identifying information about any family or family member is published on this site.
Last updated September 2026.
Open questions
What we do not know yet.
UPF3B research is still early. These are genuinely open questions, and we list them here because they are where new collaboration would help most.
Does UPF3B affect organs beyond the brain?
One report described kidney malformations in two affected brothers, but this has not been widely replicated. Whether it reflects a real part of the condition or a coincidental finding in one family remains unresolved.
How do carrier females present?
Carrier females are usually described as unaffected, but systematic assessment is rare. Some reports suggest mild features in some carriers. This is one area our own pedigree data may help clarify.
Is there a genotype-phenotype correlation?
Relatives carrying the same variant can present very differently, ranging from Lujan-Fryns syndrome to intellectual disability with no additional features. What drives that variability is not understood.
How common is UPF3B really?
Roughly 43 individuals appear in the published literature, but that number reflects who has been tested, not how many people are affected. The true prevalence is unknown and likely much higher.
ResearchStudying UPF3B or a related pathway? We would welcome a conversation.
Reach us →Publications
Published research on UPF3B.
A working list of key published papers that established and expanded what is known about UPF3B-related disorder, in order of publication year.
Tarpey et al., 2007. Nature Genetics.
The original discovery paper. A large sequencing study of families with X-linked intellectual disability found the first UPF3B variants, establishing that this gene, part of the cell's nonsense-mediated mRNA decay quality-control system, causes intellectual disability. Affected relatives in the same family ranged from Lujan-Fryns syndrome to FG syndrome to intellectual disability with no additional features.
Laumonnier et al., 2010. Molecular Psychiatry.
Screened a large cohort and identified additional UPF3B families, broadening the associated features to include autism, ADHD, and childhood-onset schizophrenia. Laboratory work in patient cells showed the variants disrupt nonsense-mediated decay, offering the first mechanistic link between the gene's normal job and the symptoms.
Lynch et al., 2012. European Journal of Medical Genetics.
A case report of two brothers who had kidney malformations (renal dysplasia) alongside their neurodevelopmental features. Important because it raised the question of whether UPF3B involvement extends beyond the brain, though this has not been widely replicated since.
Szyszka et al., 2012. Psychiatric Genetics.
Reported a UPF3B variant in a patient whose primary presentation was schizophrenia rather than intellectual disability. Adds to the evidence that UPF3B sits on a spectrum spanning developmental and psychiatric conditions.
Xu et al., 2013. Clinical Genetics.
Applied exome sequencing to a Chinese family with nonsyndromic X-linked intellectual disability and pinpointed UPF3B as the cause. Significant because it confirmed the gene's role outside the original European and Australian cohorts, and showed UPF3B can cause intellectual disability with no accompanying physical features at all.
Jolly et al., 2013. Human Molecular Genetics.
A laboratory rather than clinical study. Using patient-derived cells and neural stem cells, the authors showed that losing UPF3B function disrupts how neural progenitor cells mature and how neurons grow their branching connections. The clearest explanation to date of why an RNA quality-control defect produces brain-specific effects.
Tejada et al., 2019. Frontiers in Genetics.
A detailed study of one large Basque family spanning several generations, combining clinical descriptions, molecular testing, and carrier-female analysis. Demonstrates how much a single well-documented pedigree can add, and describes variability between affected male relatives carrying the identical variant.
Romano et al., 2024. Am. J. Medical Genetics Part A.
The most current and comprehensive review available. Combines new patients with a systematic review of all previously published cases to produce the best summary of how often each feature occurs. Also compiled the brain MRI findings, and is the source of most percentages quoted on this site.
This list reflects a broad but still non-exhaustive search of published UPF3B research. Several additional case reports are referenced inside these papers' own bibliographies, and a systematic review is still pending. Most of these journals require a subscription for the full text, so we link to PubMed rather than host copies. Tejada et al. 2019 is open access. As our own case series is published, it will be added here.