Hemophilia B: Definition, Symptoms, Treatment, and More
Mechanisms And Consequences Of Somatic Mosaicism In Humans
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Researchers Identify The Variants Responsible For A Rare And Serious Disorder
Many disorders are caused by genetic variants; to make matters worse, the genetic origin of most disorders remains unknown. Now, in a study recently published in the Journal of Clinical Immunology, researchers have shed light on the specific variants responsible for one rare and serious disorder: "RAD50 deficiency/Nijmegen breakage syndrome-like disorder."
Together with MRE11 and NBN, RAD50 is one of three proteins that make up the "MRN complex," which detects breaks in DNA and helps to initiate DNA repair. Because each of the three proteins is encoded by a separate gene, variants in any of the three genes can lead to altered functioning of the MRN complex. However, although MRE11 and NBN gene variants are known to cause other disorders, ataxia telangiectasia-like disorder and Nijmegen breakage syndrome, respectively, the pathological effects of RAD50 gene variants have remained somewhat unclear—until now.
"When we looked at the literature, we realized that only three cases of RAD50 deficiency, which leads to symptoms similar to those of Nijmegen breakage syndrome, had been reported," explains Masatoshi Takagi, lead author of the study. "Of these three, just one was reported to have RAD50 variants, with associated bone marrow failure and immunodeficiency."
When the research team came across a patient with progressive bone marrow failure and immunodeficiency combined with Nijmegen breakage syndrome-like manifestations, they decided to perform whole-exome sequencing to see if they could identify any gene variants that might lead to the observed symptoms.
"We found two different RAD50 variants in our patient, each of which was inherited from one of her parents," states Takagi. "We then tested the functional effects of these combined variants using fibroblast cells from the patient, which we grew in the lab."
The functional experiments suggested that the patient's RAD50 variants led to a loss of function of the RAD50 protein and, thus of the MRN complex. They also resulted in slower cell replication (i.E., mitosis), as expected. Interestingly, however, these variants did not cause hypersensitivity to radiation, unlike other known RAD50 variants.
"Together, the findings from our case and the three previously reported cases suggest that RAD50 deficiency/Nijmegen breakage syndrome-like disorder is characterized by growth retardation and microcephaly, which may coexist with bone marrow failure and immunodeficiency in some patients," says senior author of the study Hirokazu Kanegane. "This disorder may therefore increase susceptibility to infectious diseases and immune-related conditions."
Given the rarity of this disorder and our lack of knowledge about its genetic causes, the findings from this case are important. A better understanding of RAD50 and its effects on immunity can lead to improved diagnosis and treatment of patients with RAD50 deficiency.
More information: Masatoshi Takagi et al, Bone Marrow Failure and Immunodeficiency Associated with Human RAD50 Variants, Journal of Clinical Immunology (2023). DOI: 10.1007/s10875-023-01591-8
Citation: Researchers identify the variants responsible for a rare and serious disorder (2023, November 15) retrieved 24 November 2023 from https://medicalxpress.Com/news/2023-11-variants-responsible-rare-disorder.Html
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Are Personality Disorders Genetic? Causes And More
The exact cause of personality disorders is unclear. However, genetics, neurological differences, and environmental factors may contribute to the development of these complex mental health conditions.
Personality disorders are a class of mental health conditions marked by certain patterns of behavior, thinking, and mood. People who have personality disorders may experience distorted perceptions of reality and unusual emotional responses, which may cause distress in multiple areas of their lives.
These disorders can significantly affect a person's social functioning, relationships, and overall well-being. Both genetic and environmental factors play a role in the development of personality disorders. However, the exact relationship between genetics and these conditions is a subject of ongoing research.
In this article, we will look at whether personality disorders are genetic, as well as the causes, risk factors, disorder types, and treatments.
Personality disorders result from a combination of genetic and environmental factors. The relationship between genetics and these conditions is complex and multifaceted.
Twin studies suggest that the heritability of borderline personality disorder accounts for around 50% of a person's risk of developing it. This means that genes play a large role in whether a person develops the condition. Twin studies have also found that the heritability rate for schizoid personality disorder is 30%.
But genetics are not the only cause of personality disorders. Instead, genetics interact with environmental factors to increase or decrease the risk. Some people who have no known family history of personality disorders still develop them, and some people who have a genetic tendency toward personality disorders never develop one.
Learn more about personality disorders.
Doctors do not know the exact cause of personality disorders, but genetics may be a factor. Health experts believe that a combination of life experiences — particularly adverse childhood experiences — contributes to personality disorder development.
According to a 2016 survey of more than 1 million adults in China, people with personality disorders are more likely to be younger, unmarried, and male and to have lower socioeconomic status. These results suggest an environmental influence on the cause of these disorders.
Men are 3–5 times more likely than women to receive a diagnosis of an antisocial personality disorder, whereas borderline and histrionic personality disorders are more common in women. This indicates that genetics may play a role.
Further research is necessary to better understand the causes of personality disorders.
Understanding the risk factors associated with personality disorders is essential for recognizing and preventing these conditions. Research suggests links between genetic, social, and environmental factors, although further studies are necessary to learn more.
Risk factors for developing personality disorders include:
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