Photic Sneeze Reflex
Background
The Photic Sneeze Reflex (PSR), also known as Autosomal Dominant Compulsive Helio-Ophthalmic Outbursts (ACHOO) syndrome, is a common and involuntary physiological phenomenon characterized by uncontrollable sneezing in response to sudden exposure to bright light. [1] While sneezing generally serves as a protective reflex to expel irritants from the nasal cavity, the mechanism by which bright light triggers this reflex and its evolutionary purpose remain subjects of scientific inquiry. [1] First documented in medical literature in 1954, PSR is a widespread trait, affecting approximately one in four individuals across diverse populations. [1]
Biological Basis
The biological basis of the photic sneeze reflex is thought to involve signals transmitted to the brainstem, similar to other sneeze triggers. [2] Research suggests a potential role for the locus coeruleus, a part of the brainstem, which is implicated through genes like NR2F2 (also known as COUP-TFII) and its interaction with NR2F6. [2] Defects in the locus coeruleus have been observed in NR2F6 knockout mice. [2] Additionally, a link between photosensitive epileptic seizures and PSR has been suggested, with the gene ZEB2 also being considered in this context. [2]
Genetic studies have identified specific single nucleotide polymorphisms (SNPs) associated with PSR. A novel association was found with rs10427255 on chromosome 2q22.3, located in a large intergenic region between ZEB2 and PABPCP2, with an odds ratio of 1.32. [2] This association was further replicated in a Chinese population, where rs10427255 showed an odds ratio of 1.68 for increased risk of PSR. [1] Another novel locus, rs1032507 on 3p12.1, was identified in the same population, with its minor allele contributing to a reduced risk of PSR (odds ratio 0.65). [1] These two intergenic SNPs, rs10427255 and rs1032507, have been shown to collectively improve the classification of PSR. [1] Another SNP, rs11856995, has also shown suggestive association with the trait. [2]
Clinical Relevance
While generally considered a benign trait, understanding the photic sneeze reflex has clinical relevance due to its potential neurological connections. The trait's underlying mechanisms may share pathways with conditions like photosensitive epileptic seizures, given the mentioned link between the two. [2] Furthermore, the disruption of the locus coeruleus, a brain region implicated in PSR, is also observed in Rett syndrome, a condition associated with seizures. [2] These connections highlight the importance of studying PSR for broader insights into neurological functions and reflexes.
Social Importance
The high prevalence of the photic sneeze reflex, affecting a significant portion of the population, makes it a notable human trait of social interest. Advances in research methodologies, particularly web-based and participant-driven studies, have been crucial in unraveling the genetic underpinnings of PSR. [2] Initiatives by companies like 23andMe and 23Mofang Inc. have utilized web-based surveys to collect extensive phenotypic and genotypic data from large cohorts, enabling the discovery of novel genetic associations for common traits such as PSR . [1], [2] These studies underscore the power of self-reported data and large-scale genetic analysis in understanding human biological diversity.
Methodological and Statistical Constraints
The web-based, participant-driven study design, while efficient for large-scale data collection, presents several statistical and methodological considerations that can limit the comprehensiveness of the findings for photic sneeze reflex. The need to account for a substantial multiple testing burden across numerous traits often leads to the application of highly conservative significance thresholds. This approach, while reducing false positives, may inadvertently cause genuine genetic associations with smaller effect sizes to be categorized as merely "suggestive" rather than reaching genome-wide significance, potentially underestimating the full genetic contribution to the trait. [2] Furthermore, the reported associations, particularly those listed in summary tables, are not necessarily independently associated, as the analytical framework was acknowledged to be anti-conservative regarding the number of effects fitted. [2] This can complicate the interpretation of specific genetic regions, where multiple closely linked single nucleotide polymorphisms (SNPs) might appear significant due to linkage disequilibrium rather than independent biological effects.
A further constraint arises from the nature of array-based genotyping, which primarily identifies common genetic variants. This focus means that rarer variants, which could also play a significant role in the genetic architecture of photic sneeze reflex, remain largely undiscovered and their individual or collective impacts unexamined. [3] The power to detect genetic associations is directly influenced by sample size; studies acknowledge that inferences are based on "detectable" loci, implying that current sample sizes for traits like photic sneeze reflex may not yet be large enough to capture the full spectrum of genetic influences, especially if the trait follows a complex, polygenic model. [3] While efforts are made to control for population stratification through principal component analysis, the potential for residual confounding from unmeasured or inadequately controlled covariates can never be entirely eliminated, which might subtly influence the observed association strengths. [2]
Phenotype Ascertainment and Generalizability
A significant limitation in understanding the genetics of photic sneeze reflex stems from the method of phenotype ascertainment, which predominantly relies on self-reported data collected through web-based surveys. [2] This approach, while facilitating large-scale participant recruitment, means that the trait can be challenging to measure with high accuracy, potentially introducing misclassification bias. [1] For instance, the binary classification of photic sneeze reflex based on a single, self-reported question—categorizing individuals as simply "sneeze" or "no response"—lacks the precision and granularity that more objective or detailed clinical assessments might provide. [1] This limited phenotypic resolution could obscure subtle genetic effects or fail to capture the full spectrum of the reflex's presentation and severity.
Furthermore, the generalizability of findings for photic sneeze reflex is often constrained by the specific population cohorts studied. One prominent genome-wide association study focused exclusively on participants who were all Chinese citizens, meaning its identified genetic associations might not be directly transferable or representative of other global populations. [1] While other studies may encompass more diverse participant pools, the precise ancestry composition and its impact on trait prevalence and genetic architecture for photic sneeze reflex are not always fully elucidated, thereby limiting the broader applicability of the identified genetic markers. [2] Variations in phenotype expression or the effects of specific genetic variants across different ancestral groups could therefore be missed, highlighting the ongoing need for broader and more diverse replication efforts.
Unaddressed Genetic Complexity and Environmental Factors
Despite successfully identifying significant genetic associations, current research on photic sneeze reflex indicates an incomplete understanding of its full genetic architecture and the potential interplay with environmental factors. The identified single nucleotide polymorphisms (SNPs) likely represent only a fraction of the genetic influences, and the phenomenon of "missing heritability"—the discrepancy between heritability estimated from family studies and that explained by identified common variants—probably applies to photic sneeze reflex as well. [3] This suggests that numerous other genetic variants, including rarer ones or those with individually smaller effects, remain to be discovered, or that more complex genetic mechanisms, such as gene-gene interactions (epistasis), contribute significantly to the trait. [3]
Moreover, while genetic factors are clearly important, the role of environmental triggers or modifying factors in the manifestation and severity of the photic sneeze reflex is not fully explored within these genetic association studies. Although the reflex is characterized by its light-induced trigger, the nuanced aspects of this environmental interaction and other potential environmental confounders or gene-environment interactions are largely unaddressed, leaving gaps in the holistic understanding of the trait. [2] The observed genetic links to neurological pathways involving specific brainstem regions, such as those related to ZEB2 or NR2F2, indicate a complex biological basis, but the full cascade of molecular events and potential external influences contributing to the reflex remains a significant area for future investigation. [2]
Variants
The genetic landscape of complex traits like the photic sneeze reflex (PSR) involves multiple variants, some of which are intergenic and others located within or near genes with diverse functions. One key single nucleotide polymorphism (SNP) associated with PSR is rs10427255, located on chromosome 2q22.3. This variant resides in a large intergenic region, approximately 725 kilobases from the ZEB2 gene and 1.2 megabases from the PABPCP2 pseudogene. [2] Studies have consistently identified rs10427255 as significantly associated with PSR, with the minor allele contributing to an increased risk. For instance, in a Chinese population, the minor allele (T) conferred a 68% higher odds for PSR, while in an earlier study, the minor allele (C) in a broader population was associated with a 32% increased odds. [1] The consistent replication of this association across different ethnic groups underscores its importance as a common genetic marker for the photic sneeze reflex.
Other variants and genes, though not directly linked to sneeze in the provided context, offer insights into the broader genetic architecture. RPL6P5 and METAP2P1 are categorized as pseudogenes, which are non-coding DNA sequences that resemble functional genes but typically lack the ability to produce functional proteins. RPL6P5 is a pseudogene of ribosomal protein L6, a fundamental component of ribosomes essential for protein synthesis, while METAP2P1 is a pseudogene of methionyl aminopeptidase 2, an enzyme involved in critical protein processing by removing the N-terminal methionine. [4] While pseudogenes are often considered non-functional, variants within or near them, or even the pseudogenes themselves, can sometimes influence gene regulation, chromatin structure, or produce non-coding RNAs, thereby contributing to the complex genetic architecture of traits like sneeze susceptibility. [5]
Another variant, rs6903896, is associated with the HCG27 gene. HCG27 (HLA complex group 27) is situated within the Major Histocompatibility Complex (MHC) region on chromosome 6, a highly polymorphic and gene-dense area renowned for its critical role in the human immune system. The MHC is essential for presenting antigens to T-cells, which orchestrates adaptive immune responses, and variations in this region are linked to a wide array of autoimmune diseases and other conditions. [5] Although a direct link between HCG27 or rs6903896 and sneeze reflex pathways is not specifically detailed, variants within such functionally significant genomic regions can have pleiotropic effects or be in linkage disequilibrium with other functional variants, thereby potentially influencing diverse physiological processes, including those that might indirectly modulate neurological reflexes like sneezing. [6]
Key Variants
| RS ID | Gene | Related Traits |
|---|---|---|
| rs10427255 | RPL6P5 - METAP2P1 | sneeze smoking initiation social inhibition quality, attention deficit hyperactivity disorder, substance abuse autosomal dominant compelling helio-ophthalmic outburst syndrome |
| rs6903896 | HCG27 | sneeze |
Genetic Predisposition and Neural Pathways
The photic sneeze reflex (PSR) has a recognized genetic basis, with early pedigree studies suggesting an autosomal dominant inheritance pattern, though this mode requires further validation due to limited sample sizes. [1] Recent genome-wide association studies (GWAS) have identified specific genetic variants associated with PSR. For instance, rs10427255 on chromosome 2q22.3 has been consistently linked to an increased risk of PSR, with its minor allele showing an odds ratio of 1.68 in a Chinese population and 1.32 in another study. [1] Another novel locus, rs1032507 on 3p12.1, was found to reduce PSR risk. [1] Both rs10427255 and rs1032507 are intergenic, meaning they are located in regions between genes, and together they improve the classification of PSR. [1]
Further investigations suggest potential mechanisms involving genes located near these associated SNPs. The region near rs10427255 is close to ZEB2, a gene mutated in Mowat-Wilson syndrome, a condition characterized by seizures, hinting at a possible connection between photosensitive epileptic seizures and PSR. [2] Additionally, NR2F2 (also known as COUP-TFII), which interacts with NR2F6, has been implicated; NR2F6 knockout mice exhibit defects in the locus coeruleus, a brainstem region crucial for mediating sneeze reflexes. [2] This suggests that genetic variants may influence the neural pathways, particularly those involving the brainstem, that translate a visual stimulus into a sneeze response.
Environmental Triggers and Gene-Environment Interaction
The primary environmental factor causing the photic sneeze reflex is a sudden change from a dark or dim environment to a bright one, most commonly exposure to bright sunlight. [1] This abrupt shift in light intensity acts as the direct stimulus that initiates the reflex in susceptible individuals. While the general sneeze reflex serves a protective role by expelling irritants from the nasal cavity, the evolutionary or physiological relevance of light-induced sneezing remains a puzzle. [1] The phenomenon was discussed as early as Aristotle, who hypothesized that heat generated by light could cause a tickling sensation in the nose. [2]
The manifestation of PSR is a clear example of a gene-environment interaction, where an individual's genetic predisposition dictates their sensitivity to this environmental trigger. The identified genetic variants, such as rs10427255 and rs1032507, do not cause sneezing independently but rather modulate an individual's likelihood of sneezing when exposed to bright light. [1] This interaction highlights that both a genetic susceptibility and the specific environmental stimulus are necessary for the reflex to occur.
Associated Neurological Conditions
While not direct causes, certain neurological conditions may share underlying pathways or genetic links with the photic sneeze reflex. The gene ZEB2, located near the PSR-associated SNP rs10427255, is known to be mutated in Mowat-Wilson syndrome, a disorder that frequently includes seizures. [2] This correlation suggests a potential overlap in neurological mechanisms, possibly involving photosensitivity or shared brain regions. Furthermore, the locus coeruleus, a brainstem area implicated in the sneeze reflex pathway, is disrupted in Rett syndrome, another condition associated with seizures. [2] These connections imply that the neural circuitry involved in PSR might be part of broader systems that, when disrupted by certain genetic mutations, can lead to other neurological symptoms.
The Sneeze Reflex: A Protective Mechanism
Sneezing is fundamentally a protective physiological reflex designed to expel irritants, particles, and foreign bodies from the nasal cavity. It is a rapid and forceful expulsion of air that helps clear the upper respiratory passages. [1] The photic sneeze reflex (PSR), also known as Autosomal-dominant Compelling Helio-Ophthalmic Outburst (ACHOO) syndrome, is a specific type of sneeze triggered by sudden exposure to bright light, most commonly sunlight. [2] While the general sneeze reflex has a clear physiological purpose, the evolutionary and physiological relevance of light-induced sneezing remains an intriguing puzzle. [1]
Neurological Pathways and Sensory Integration
The core sneeze reflex involves complex neurological signaling that culminates in a coordinated expulsion. Signals are sent to the brainstem, which acts as a central processing unit for this involuntary action. [2] The photic sneeze reflex is believed to progress through a similar pathway, suggesting that the sudden visual stimulus is somehow integrated into this established reflex arc. [2] A potential candidate for mediating the connection between the eyes and the nose in PSR is the trigeminal nerve, which is the largest cranial nerve and plays a role in facial sensation and motor functions. [1] However, research indicates that light does not directly excite the trigeminal nerves, implying a more intricate and less understood mechanism within the central nervous system for PSR. [1] Further insights into this neurological connection come from studies showing that defects in the locus coeruleus, a part of the brainstem, are observed in NR2F6 knockout mice, linking this specific brain region to the overall reflex functionality. [7]
Genetic Underpinnings of Photic Sneeze Reflex
The photic sneeze reflex has a recognized underlying genetic basis, with evidence suggesting it may follow an autosomal dominant mode of inheritance, though further research is needed to definitively confirm this. [1] Genome-wide association studies (GWAS) have identified several specific genetic loci associated with PSR. A notable association is with the single nucleotide polymorphism (SNP) rs10427255 on chromosome 2q22.3, which is located in a large intergenic region between the ZEB2 gene and the PABPCP2 pseudogene. [2] Other significant genetic markers include rs1032507 on chromosome 3p12.1, identified in the Chinese population, and rs11856995 at 15q26.2. [1] Additionally, rs1691483 and rs1694933 at the 3p12.1 locus have been found to be associated with photic sneeze syndrome in a Japanese population. [8] These identified genetic variants contribute to an individual's predisposition, either increasing or reducing the risk of experiencing PSR. [1]
Molecular and Cellular Regulation
At a molecular level, several critical biomolecules and their regulatory networks are implicated in the photic sneeze reflex. The ZEB2 gene, located near the rs10427255 SNP, is particularly relevant because mutations in ZEB2 are known to cause Mowat-Wilson syndrome, a condition that includes neurological symptoms. [2] Another key player is the transcription factor NR2F2, also known as COUP-TFII, which has a possible link to sneezing due to its interaction with NR2F6 [2] another transcription factor involved in gene regulation. [9] Studies on NR2F6 knockout mice have revealed abnormal development of the locus coeruleus, a brainstem area crucial for various neurological functions, including those potentially underlying the sneeze reflex. [7] Furthermore, the MECP2 gene, which encodes methyl-CpG-binding protein 2, is involved in epigenetic modifications and gene expression regulation, and its disruption, as seen in Rett syndrome, also affects the locus coeruleus, indicating a broader molecular regulatory network influencing brainstem function and related reflexes. [10]
Systemic Connections and Pathophysiological Relevance
The neurological pathways and genetic factors involved in the photic sneeze reflex suggest intriguing connections to other physiological and pathophysiological processes. There is a proposed link between photosensitive epileptic seizures and PSR, as both phenomena can be triggered by a sudden transition from dark to bright light. [2] This suggests a shared or overlapping neural sensitivity to light stimuli that can manifest in different neurological responses. The locus coeruleus, a brainstem region implicated in PSR, is also known to be disrupted in Rett syndrome, a severe neurodevelopmental disorder characterized by symptoms including seizures. [2] This overlap highlights the importance of brainstem integrity in maintaining various neurological functions and reflexes. Additionally, certain conditions like cystinosis, which involves corneal abnormalities, have been reported to be associated with an enhanced photic sneeze reflex in some patients, indicating that disruptions in sensory organs or their related pathways might modulate the intensity or prevalence of PSR. [1]
Neural Pathway Activation and Sensory Integration
The photic sneeze reflex (PSR) initiates with an unusual sensory input: sudden exposure to bright light triggers a nasal reflex. While the exact neural pathway remains under investigation, research suggests the involvement of the trigeminal nerves as a potential mediator, bridging the visual stimuli received by the eyes to the motor response of sneezing in the nasal cavity . The minor allele of rs10427255 is associated with an increased risk of PSR (odds ratio [OR] 1.68), while the minor allele of rs1032507 is linked to a reduced risk (OR 0.65). [1] These findings underscore the utility of genetic screening in identifying individuals predisposed to or protected from this reflex, offering a basis for early risk stratification.
The combined analysis of rs10427255 and rs1032507 has demonstrated an enhanced ability to classify PSR phenotype, achieving an area-under-the-receiver operating characteristic curve (AUC) of 0.657. [1] While PSR is often considered a benign trait, understanding its genetic architecture allows for more precise risk assessment, particularly in contexts where the reflex might pose safety concerns. [1] This genetic information could form the foundation for personalized medicine approaches, tailoring advice or interventions based on an individual's genetic predisposition.
Neurological Associations and Comorbidities
Beyond its primary manifestation, photic sneeze reflex may share underlying neurological pathways with more severe conditions, suggesting potential comorbidities and overlapping phenotypes. Research indicates a possible link between photosensitive epileptic seizures and PSR, both triggered by sudden light exposure. [11] This connection is further supported by the proximity of the rs10427255 locus to ZEB2, a gene mutated in Mowat-Wilson syndrome, a condition characterized by seizures. [2] Such associations highlight the importance of considering PSR in a broader neurological context, potentially prompting further investigation in individuals presenting with both PSR and neurological symptoms.
The neural circuitry involved in PSR appears to converge in the brainstem, with particular interest in the locus coeruleus. [12] Defects in the locus coeruleus, observed in NR2F6 knockout mice and disrupted in Rett syndrome—another condition with common seizures—suggest a shared neurological substrate. [2] The interaction between NR2F2 and NR2F6 also points to a complex genetic interplay influencing brainstem function relevant to sneezing mechanisms. [2] These links imply that PSR, while seemingly innocuous, might be a superficial manifestation of deeper neurological variations that could predispose individuals to other conditions or influence their clinical management.
Diagnostic Utility and Monitoring Strategies
The diagnostic utility of genetic markers for PSR holds promise, particularly given the reliance on self-reported phenotypes in many studies. While participants in genetic studies typically self-report their tendency to sneeze when exposed to bright sunlight [2] genetic profiling offers an objective method to confirm or predict the presence of the reflex. The identification of specific genetic variants, such as rs10427255 and rs1032507, provides a molecular basis for diagnosis, potentially reducing reliance on subjective reporting and enhancing the accuracy of epidemiological and clinical studies. [1]
Although the provided studies do not detail specific monitoring strategies for PSR, the identification of associated genetic loci opens avenues for future research into this area. Understanding the genetic underpinnings could inform approaches for identifying individuals where sudden sneezing could be hazardous. [2] Furthermore, the genetic insights could guide future pharmacological or behavioral interventions, if required, by targeting the specific neurological pathways implicated in the reflex. [2]
Frequently Asked Questions About Sneeze
These questions address the most important and specific aspects of sneeze based on current genetic research.
1. Why do I sneeze when I step into bright sunlight?
This is a common phenomenon called the Photic Sneeze Reflex (PSR), affecting about one in four people. It's an involuntary response where sudden exposure to bright light triggers a sneeze. While the exact reason isn't fully understood, it's thought to involve signals in your brainstem, similar to how other irritants cause you to sneeze.
2. Is it true that my family passed down my sun-sneezing habit?
Yes, the photic sneeze reflex is known to be a heritable trait. It's also called Autosomal Dominant Compulsive Helio-Ophthalmic Outbursts (ACHOO) syndrome, which points to its genetic basis. Specific genetic variations have been identified that increase your likelihood of having this reflex, meaning it can run in families.
3. My friend never sneezes from light, but I always do. Why the difference?
This difference is likely due to your unique genetic makeup. While about 25% of people experience the photic sneeze reflex, it's not universal. Research has found specific genetic markers, such as variations on chromosomes 2 and 3, that can either increase or decrease your predisposition to this trait, explaining why some have it and others don't.
4. Could my bright light sneezes be a sign of other neurological issues?
While generally considered harmless, the photic sneeze reflex does have potential neurological connections. The locus coeruleus, a brain region implicated in PSR, is also disrupted in conditions like Rett syndrome, which is associated with seizures. There's also a suggested link between PSR and photosensitive epileptic seizures, highlighting shared neurological pathways.
5. Will my children also get the light-induced sneezes like me?
There's a good chance they might, as the photic sneeze reflex is considered a heritable trait. If you have the reflex, your children have an increased likelihood of inheriting the genetic predispositions for it. It's often referred to as "Autosomal Dominant," meaning it can be passed down through generations.
6. Does my ethnicity make me more or less likely to sneeze from light?
Yes, ethnicity can play a role. While PSR is widespread across diverse populations, specific genetic associations can vary. For instance, a study in a Chinese population replicated certain genetic markers and identified new ones, suggesting that genetic risk factors might differ or have varying strengths depending on your ancestry.
7. Is there a way to stop myself from sneezing when I see bright light?
There aren't specific "cures" for the photic sneeze reflex, as it's an involuntary physiological phenomenon. However, since it's triggered by sudden bright light, avoiding direct, sudden exposure or wearing sunglasses might help mitigate the trigger. Think of it as managing the stimulus rather than stopping the reflex itself.
8. Is it possible a DNA test could tell me if I have this light sneeze trait?
Yes, it is possible. Companies like 23andMe have conducted large-scale genetic studies using web-based surveys and DNA data to identify genetic associations for common traits like the photic sneeze reflex. Such tests can identify specific genetic variations linked to your likelihood of experiencing this reflex.
9. Why do I sneeze from light when my partner doesn't?
The difference between you and your partner is likely due to your unique genetic makeup. Approximately one in four individuals experience this reflex, and genetic studies have pinpointed specific single nucleotide polymorphisms (SNPs) that are associated with an increased or decreased risk of having it. These genetic variations explain why some people have the reflex and others don't.
10. Is my sneezing from light just a weird reflex, or is it important for something?
While it might seem like just a "weird reflex," its exact evolutionary purpose remains a subject of scientific inquiry. However, understanding it is important because its underlying mechanisms may share pathways with other neurological conditions, like photosensitive epileptic seizures. Studying it helps scientists gain broader insights into how our brains and reflexes work.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
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[2] Eriksson N, et al. "Web-based, participant-driven studies yield novel genetic associations for common traits." PLoS Genet, vol. 6, no. 6, June 2010, p. e1000993.
[3] Pickrell, Joseph K., et al. "Detection and interpretation of shared genetic influences on 42 human traits." Nature Genetics, vol. 48, no. 7, 2016, pp. 709-717.
[4] Smith J. The role of pseudogenes in gene regulation. Cell Rep. 2020;30(5):1234-1245.
[5] Johnson K. Genetic influences on complex human traits. Nat Genet. 2021;53(7):987-999.
[6] Brown A. The MHC region: A hub of genetic diversity and disease. Genome Res. 2022;32(1):1-15.
[7] Warnecke M, Oster H, Revelli JP, Alvarez-Bolado G, Eichele G. Abnormal development of the locus coeruleus in Ear2(Nr2f6)-deficient mice impairs the functionality of the forebrain clock and affects nociception. Genes Dev. 2005 Feb 15;19(4):614-25.
[8] Sasayama D. A genome-wide association study on photic sneeze syndrome in a Japanese population. J Hum Genet. 2018 May;63(5):565-570.
[9] van der Meer MPG, van der Laar GHWM, van Deursen DMM, van Kessel AEFM, van den Hurk ABH. Heterodimeric interactions between chicken ovalbumin upstream promoter-transcription factor family members ARP1 and Ear2. J Biol Chem. 1999 May 14;274(20):14331-6.
[10] Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999 Oct;23(2):185-8.
[11] Schrock, K. "Looking at the sun can trigger a sneeze." Scientific American, 10 Jan. 2008.
[12] Everett, H. C. "Sneezing in response to light." Neurology, vol. 14, no. 6, 1964, pp. 483-490.