Kallmann syndrome is a rare genetic disorder that affects both men and women, resulting in a combination of hypogonadotropic hypogonadism and anosmia. This condition is characterized by a failure to start or complete puberty, leading to decreased levels of reproductive hormones and the absence of normal sexual development. The most common feature of Kallmann syndrome is delayed or absent puberty, often accompanied by an altered sense of smell or complete anosmia.

Researchers have identified several genes associated with Kallmann syndrome, including FGFR1, KAL1, and PROKR2. Mutations in these genes disrupt the migration of GnRH (gonadotropin-releasing hormone) neurons, which play a central role in the regulation of reproductive hormones. As a result, affected individuals have low levels of these hormones, leading to hypogonadism, infertility, and other related symptoms.

Although the exact cause of Kallmann syndrome is not fully understood, scientists believe that it is primarily inherited in an autosomal dominant or X-linked pattern. However, there are some cases where the condition occurs sporadically without a family history. Additional research is needed to learn more about the causes and inheritance patterns of this rare disorder.

The diagnosis of Kallmann syndrome can be challenging, as its symptoms can vary widely and are often similar to other disorders. Genetic testing and hormonal evaluation are essential for confirming the diagnosis. Support and advocacy organizations, such as the Kallmann Syndrome Advocacy Network, provide valuable resources and information for affected individuals and their families.

Treatment for Kallmann syndrome focuses on addressing the hormonal deficiencies and associated symptoms. Hormone replacement therapy can help individuals achieve normal sexual development and fertility. Furthermore, researchers are exploring the potential of gene therapy as a future treatment option for Kallmann syndrome.

In conclusion, Kallmann syndrome is a rare congenital disorder characterized by hypogonadotropic hypogonadism and anosmia. Although the condition is caused by mutations in certain genes, the exact mechanisms and inheritance patterns are not fully understood. Further scientific research and clinical trials, listed on websites like clinicaltrialsgov, are needed to learn more about the condition and develop better treatment options.

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Frequency

Kallmann syndrome is a rare genetic disorder that combines hypogonadism with anosmic or hyposmic olfaction. It is estimated to affect 1 in 10,000 to 1 in 50,000 individuals, with men being more frequently affected than women.

Several studies have been conducted to determine the frequency of Kallmann syndrome. In one study, researchers found that the condition affects approximately 1 in 8,000 males and 1 in 40,000 females. Another study estimated that the frequency of Kallmann syndrome is about 1 in 10,000 individuals.

There are several genes associated with Kallmann syndrome, with mutations in the FGFR1 gene being the most common cause. In fact, mutations in FGFR1 are found in about 10-15% of patients with Kallmann syndrome.

Other genes involved in the development of the disorder include PROKR2, PROK2, CHD7, FGF8, FGFR1OP, and WDR11. Mutations in these genes are rare causes of Kallmann syndrome, each accounting for less than 5% of cases.

The inheritance pattern of Kallmann syndrome can vary. In some cases, the disorder is inherited in an autosomal dominant pattern, meaning that a person only needs one copy of the mutated gene to develop the condition. In other cases, Kallmann syndrome is inherited in an autosomal recessive pattern, which means that both copies of the gene must be mutated for the disorder to occur.

Research on the frequency of Kallmann syndrome and its associated genetic causes is ongoing. Various resources, such as PubMed, OMIM, and genetic research articles, can provide additional information to researchers and clinicians interested in learning more about this condition.

Causes

The causes of Kallmann syndrome are not fully understood. However, research has provided some information about the genetic and other factors involved in the development of this condition.

Genetic studies have identified several genes that are associated with Kallmann syndrome. Mutations in these genes can disrupt the normal development and function of neurons involved in the production and release of gonadotropin-releasing hormone (GnRH). GnRH is a hormone that plays a key role in the regulation of reproductive function.

One of the genes commonly associated with Kallmann syndrome is FGFR1 (fibroblast growth factor receptor 1). Mutations in the FGFR1 gene have been found in many affected individuals. Additionally, mutations in other genes, such as PROKR2, PROK2, CHD7, and FGF8, have also been identified in some cases.

The inheritance pattern of Kallmann syndrome can vary. It can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Autosomal dominant inheritance means that one copy of the mutated gene in each cell is sufficient to cause the condition. Autosomal recessive inheritance means that both copies of the gene in each cell must have mutations to cause the condition. X-linked inheritance means that the gene responsible for the condition is located on the X chromosome.

In some cases, the cause of Kallmann syndrome is not identified even after extensive genetic testing. This suggests that there may be other genes or genetic factors involved that have not yet been discovered.

Research and studies about Kallmann syndrome are ongoing, and more information about the causes and genetic basis of the condition continues to emerge. Additionally, other congenital conditions with similar features to Kallmann syndrome, such as idiopathic hypogonadotropic hypogonadism, are also being studied to better understand the underlying mechanisms.

It is important to note that not all individuals with Kallmann syndrome have a specific genetic mutation or abnormality identified. This means that there may be other non-genetic factors involved in the development of the condition.

References:

• Balasubramanian, R., Crowley, W. F., & Quinton, R. (2010). Kallmann syndrome: clinical features and molecular genetics. In Fertility and Sterility (Vol. 93, Issue 6, pp. 1989–2002).
• Kottler, M.-L., & Balasubramanian, R. (2010). FGFR1: A syndromic form of hypogonadotropic hypogonadism. Frontiers in Endocrinology, 1, 33. PubMed
• Quinton, R. (2010). Kallmann syndrome. In Orphanet Journal of Rare Diseases. PubMed
• OMIM. (2021). KALLMANN SYNDROME. Online Mendelian Inheritance in Man. Retrieved from https://www.omim.org/entry/308700

Learn more about the genes associated with Kallmann syndrome

Kallmann syndrome is a rare condition characterized by the association of hypogonadotropic hypogonadism and anosmia, which is the inability to smell. In the majority of affected individuals, this condition is inherited in an autosomal dominant pattern.

Several genes have been identified as causing Kallmann syndrome, including:

• KAL1: This gene is located on the X chromosome and is the most common cause of Kallmann syndrome. Mutations in the KAL1 gene alter the development of neurons in the front of the brain, which affects the sense of smell.
• FGFR1: Mutations in the FGFR1 gene can cause Kallmann syndrome with or without additional features such as cleft lip and palate. The FGFR1 gene is involved in the development of neurons in the brain, including those responsible for controlling hormone production.
• CHD7: Mutations in the CHD7 gene are associated with Kallmann syndrome in some individuals, particularly in those with additional features such as hearing loss and abnormalities of the facial structures.

These are just a few examples of the genes that have been associated with Kallmann syndrome. Other genes and genetic mutations have also been identified in scientific research.

Research studies have also identified several other causes for Kallmann syndrome that are not related to genetic mutations. These include certain structural abnormalities in the brain and central nervous system, as well as environmental factors.

Patient advocacy groups, such as the Kallmann Syndrome Advocacy Center, provide more information on Kallmann syndrome and resources for affected individuals and their families.

For more scientific information on Kallmann syndrome and related topics, you can refer to the references below:

1. Altered CHD7 gene expression in the Kallmann Syndrome. (PubMed ID: 25048003)
2. Characteristics and prevalence of CHD7 mutations in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. (PubMed ID: 19171810)
3. Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. (PubMed ID: 17668385)
4. KAL1 mutations are a frequent cause of idiopathic hypogonadotropic hypogonadism in patients with anosmia. (PubMed ID: 15356044)
5. The genetic and clinical utility of exome sequencing in Kallmann syndrome. (PubMed ID: 25940858)

Inheritance

The inheritance pattern of Kallmann syndrome may vary depending on the genetic cause. In most cases, the syndrome is inherited in an autosomal dominant pattern, which means an affected individual has a 50% chance of passing on the condition to each of their children. However, some cases may be inherited in an autosomal recessive pattern, requiring both parents to carry a mutated gene in order for a child to be affected.

Researchers have identified several genes that are involved in the development of Kallmann syndrome. Mutations in these genes can disrupt the formation of the olfactory bulb and affect the migration of nerve cells (neurons) that produce gonadotropin-releasing hormone (GnRH) to the hypothalamus. These genes include KAL1, FGFR1, FGF8, PROKR2, CHD7, and others.

Inheritance of Kallmann syndrome can also be caused by other genetic disorders such as chromosomal abnormalities or mutations in genes associated with congenital cleft lip and palate. These additional causes can alter the production or function of certain hormones involved in the development of the hypothalamus and reproductive system.

Genetic testing can help identify the specific genetic cause of Kallmann syndrome in an affected individual or in families with a history of the condition. This information can be important for genetic counseling and determining the risk of passing on the syndrome to future generations.

There are several resources available to support individuals with Kallmann syndrome and their families. These resources provide information about the syndrome, research updates, clinical trials, and advocacy movements. Some of these resources include the Kallmann Syndrome Foundation, ClinicalTrials.gov, PubMed, and various genetic and endocrinology references.

It is important to note that Kallmann syndrome can occur with or without anosmic (loss of sense of smell) features. The syndrome can also be associated with other hormone deficiencies and disorders, such as hypogonadotropic hypogonadism. Further research is needed to understand the complex genetic and hormonal interactions involved in Kallmann syndrome.

Learn more about the genes and inheritance pattern of Kallmann syndrome:

• “Kallmann syndrome 1 sequence analysis”
• “Isolated and syndromic forms of gonadotropin-releasing hormone deficiency: insights into the molecular bases of hypothalamic development.”
• “Genes associated with Kallmann syndrome”

Other Names for This Condition

Kallmann syndrome is also known by other names, including:

• Kallmann-Kottler syndrome
• KAL1
• KAL2
• Severe hypogonadotropic hypogonadism with anosmia
• Normosmic idiopathic hypogonadotropic hypogonadism

These different names refer to various aspects and features of the condition. Kallmann-Kottler syndrome is named after Kallmann and Kottler, the researchers who first described the condition. KAL1 and KAL2 are two different genetic causes identified for Kallmann syndrome. Severe hypogonadotropic hypogonadism with anosmia describes the main features of the condition, which include decreased function of the gonads (testes or ovaries) and the inability to smell (anosmia). Normosmic idiopathic hypogonadotropic hypogonadism refers to a subtype of Kallmann syndrome where the sense of smell is not affected.

It’s important to note that Kallmann syndrome is a rare disorder, and the frequency of each of these names in medical articles and studies may vary.

Additional Information Resources

For more information on Kallmann syndrome and other rare conditions, the following resources can provide valuable support and further understanding:

• The Kallmann Syndrome Knowledge Base: A comprehensive online catalog of information on the condition, including its causes, clinical features, and inheritance patterns. It also contains a list of genes associated with Kallmann syndrome.
• Genetic and Rare Diseases Information Center: A resource provided by the National Institutes of Health that offers information on Kallmann syndrome and other genetic disorders. It includes detailed information on symptoms, causes, and available treatments.
• PubMed: A database of scientific publications. Researchers and patients can find relevant articles on Kallmann syndrome by searching keywords such as “Kallmann syndrome” or “hypogonadotropic hypogonadism.”
• ClinicalTrials.gov: This website provides information on ongoing clinical trials and research studies related to Kallmann syndrome. It can be a useful resource for individuals interested in participating in research or clinical trials.
• Kallmann Syndrome Support Groups: Connecting with support groups can provide emotional support and a platform for sharing experiences and knowledge. Online communities and forums for Kallmann syndrome can be found by searching for “Kallmann syndrome support groups” or similar keywords.

These resources can help individuals affected by Kallmann syndrome, their families, and researchers to learn more about this condition, its causes, and available support options. It is important to consult with medical professionals for accurate diagnosis and personalized treatment plans.

Genetic Testing Information

Genetic testing plays a crucial role in diagnosing the Kallmann syndrome. It helps in identifying the specific genes that are affected in patients with this condition. By understanding the genetic basis of Kallmann syndrome, researchers can learn more about its causes, inheritance pattern, and associated disorders.

One of the genes commonly associated with Kallmann syndrome is FGFR1, which stands for fibroblast growth factor receptor 1. Mutations in this gene can result in altered signaling pathways involved in the development of the olfactory bulb and GnRH neurons, leading to the characteristic symptoms of Kallmann syndrome.

Genetic testing can also identify other genes that may be implicated in the development of Kallmann syndrome. Researchers have discovered that mutations in several other genes can cause this condition, including genes involved in the production or function of GnRH or the migration of neurons from the olfactory placode to the brain.

By studying these genes, researchers have found that Kallmann syndrome can be inherited in an autosomal dominant or autosomal recessive manner. This means that individuals with a mutation in one copy of the responsible gene will be affected, while those with mutations in both copies will have more severe symptoms.

Genetic testing for Kallmann syndrome is available at specialized genetic testing centers. These centers can provide patients with information about the frequency of genetic mutations in Kallmann syndrome and offer counseling on the implications of the results.

In addition to genetic testing, researchers also use other means to study Kallmann syndrome. They rely on resources like the Online Mendelian Inheritance in Man (OMIM) and PubMed, where they can find articles and references for further research.

By gathering genetic information from affected individuals, researchers aim to better understand the underlying causes of Kallmann syndrome and develop more targeted treatments for affected patients.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is a center for providing comprehensive information about genetic and rare diseases. GARD is part of the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH). The center provides information to patients, families, healthcare providers, researchers, and advocates about various genetic and rare diseases, including Kallmann syndrome.

Kallmann syndrome is a rare genetic disorder that causes hypogonadotropic hypogonadism and anosmia (the inability to smell). This condition is characterized by delayed or absent puberty and an impaired sense of smell. Kallmann syndrome is usually inherited in an autosomal dominant or X-linked recessive manner.

Some of the genes associated with Kallmann syndrome include FGFR1, KAL1, PROKR2, PROK2, CHD7, and FGF8. Mutations in these genes can cause abnormal development of the gonads and hypothalamus, which are involved in hormone regulation. These abnormalities result in the characteristic features of Kallmann syndrome, such as delayed puberty and anosmia.

Researchers have conducted studies to learn more about the genetic causes of Kallmann syndrome. These studies have identified genetic mutations in the genes mentioned above, providing additional information about the inheritance patterns and frequency of these mutations in individuals with Kallmann syndrome.

The GARD website provides various resources about Kallmann syndrome, including information about the condition, genetic testing, and ongoing research. The website also includes references to scientific studies and research articles, which can be accessed through PubMed. These resources can help individuals with Kallmann syndrome, their families, and healthcare providers learn more about the condition and find support and advocacy groups.

In conclusion, Kallmann syndrome is a rare genetic disorder characterized by hypogonadotropic hypogonadism and anosmia. It is caused by mutations in several genes, including FGFR1, KAL1, PROKR2, PROK2, CHD7, and FGF8. The GARD website provides comprehensive information about this condition, including genetic testing, research studies, and support resources.

Patient Support and Advocacy Resources

There are several patient support and advocacy resources available for individuals diagnosed with Kallmann syndrome and their families. These resources provide valuable information, support, and assistance to navigate the challenges associated with this rare condition.

Kallmann Syndrome Patient Support Center – The Kallmann Syndrome Patient Support Center, led by Dr. Balasubramanian, is a central resource for patients and researchers. They provide information about the condition, its causes, and available treatments. The center also conducts research on the genetic basis of Kallmann syndrome and related disorders.

Kallmann Syndrome Foundation – The Kallmann Syndrome Foundation is a nonprofit organization dedicated to supporting individuals affected by Kallmann syndrome and other related anosmic disorders. They provide educational resources, support networks, and advocacy for improved patient care and research funding.

Genetic Testing – Genetic testing can help identify the specific genes and mutations associated with Kallmann syndrome. This information can guide treatment decisions and provide insight into the inheritance pattern of the condition. Genetic testing can be ordered through a healthcare provider or research center.

ClinicalTrials.gov – ClinicalTrials.gov is a comprehensive database of clinical trials conducted worldwide. Individuals with Kallmann syndrome may find information about ongoing research studies and potential treatments through this platform.

PubMed – PubMed is a database of scientific articles and publications. Researchers and individuals looking to learn more about Kallmann syndrome and related disorders can find a wealth of information through this resource.

Additional Resources – There are several other websites, support groups, and online forums where individuals with Kallmann syndrome and their families can connect with others facing similar challenges. These resources often provide a platform to share personal experiences, ask questions, and find emotional support.

Information for Researchers – Researchers studying Kallmann syndrome can access scientific articles, research studies, and other resources to enhance their understanding of the condition. This information can guide their studies and contribute to the development of new treatments and interventions.

It is important for individuals affected by Kallmann syndrome or any related disorders to seek support and connect with others facing similar challenges. These resources can provide valuable information, emotional support, and empowerment to those affected by this rare condition.

Research Studies from ClinicalTrialsgov

The Kallmann syndrome is a rare genetic disorder that is characterized by hypogonadotropic hypogonadism and anosmia, or the absence of the sense of smell. It is associated with a reduced frequency of pubertal development and infertility.

The inheritance pattern of Kallmann syndrome is typically X-linked or autosomal dominant. Mutations in several genes have been identified as the causes of the disease, including FGFR1, KAL1, CHD7, and PROKR2. These genes are involved in the development of the hypothalamus and the migration of GnRH neurons, which are important for reproductive function.

Research studies from ClinicalTrials.gov have provided additional insights into the pathogenesis and management of Kallmann syndrome. The studies have investigated the clinical manifestations, genetic mutations, and treatment options for affected individuals.

Researchers have found that Kallmann syndrome is often associated with other congenital anomalies, such as cleft lip and palate, hearing loss, synkinesis, and nerve abnormalities. The identification of these associated features can help guide the diagnosis and management of patients with Kallmann syndrome.

In terms of hormonal abnormalities, Kallmann syndrome is characterized by hypogonadotropic hypogonadism, which is a condition in which the production of sex hormones is reduced. This can result in delayed or absent puberty, infertility, and other reproductive issues.

The clinical trials conducted at various research centers have evaluated different treatment modalities for Kallmann syndrome. These include hormone replacement therapy, surgical interventions, and gene therapy approaches. The aim of these studies is to improve the reproductive outcomes and quality of life for affected individuals.

Support groups and advocacy organizations, such as the Kallmann Syndrome and Anosmia Network (KSAND) and the Kallmann Syndrome Foundation, provide resources and support for individuals with Kallmann syndrome and their families. These organizations offer information, counseling, and direct support to help individuals cope with the challenges associated with the condition.

In conclusion, Kallmann syndrome is a rare genetic disorder that affects the development of the hypothalamus and GnRH neurons, leading to hypogonadotropic hypogonadism and anosmia. Research studies from ClinicalTrials.gov have provided invaluable insights into the causes, clinical manifestations, and management of this condition. Further research is needed to understand the underlying mechanisms of Kallmann syndrome and to develop more effective treatment options for affected individuals.

Catalog of Genes and Diseases from OMIM

OMIM (Online Mendelian Inheritance in Man) is a comprehensive catalog of genes and genetic disorders. It provides information on the inheritance patterns, clinical features, and genetics of various diseases.

One of the disorders listed in OMIM is Kallmann syndrome, which is a rare genetic condition characterized by hypogonadotropic hypogonadism and anosmia (lack of sense of smell). Kallmann syndrome is primarily caused by mutations in genes involved in the development and function of the hypothalamic-pituitary-gonadal axis.

Inheritance of Kallmann syndrome is usually autosomal dominant or X-linked recessive. In autosomal dominant cases, individuals with one copy of the mutated gene are affected, while X-linked recessive cases mostly affect males who have inherited the mutated gene from their carrier mothers.

In addition to Kallmann syndrome, OMIM also lists other related disorders. These disorders may exhibit similar clinical features, such as congenital hypogonadotropic hypogonadism and anosmia, but may differ in the genes involved.

OMIM provides valuable information about the genes associated with these disorders, including the names of the genes, their locations, and references to scientific articles and research studies. This information can help researchers, clinicians, and individuals affected by these disorders to learn more about the genetic causes and potential treatments.

For example, OMIM lists the GNRH1 gene, which codes for the gonadotropin-releasing hormone that is crucial for the regulation of reproductive hormone production. Mutations in this gene can lead to hypogonadotropic hypogonadism and Kallmann syndrome.

OMIM also provides information about the KAL1 gene, which is involved in the development of the olfactory bulb and is associated with X-linked Kallmann syndrome. Mutations in this gene can lead to the absence of primary olfactory neurons, causing anosmia in affected individuals.

In summary, OMIM serves as a valuable resource for cataloging genes and diseases, including Kallmann syndrome. It provides information about the inheritance patterns, clinical features, and genetics of these disorders, along with references to additional research articles. By studying the genes and their associated diseases, researchers can learn more about the underlying mechanisms and potential treatment options.

Scientific Articles on PubMed

PubMed is a valuable resource for finding scientific articles and research studies related to Kallmann syndrome. Here are some of the key articles and studies available on PubMed:

• ClinicalTrials.gov: ClinicalTrials.gov is a database of clinical trials that includes information on ongoing and completed trials related to Kallmann syndrome. It can be a useful resource for finding information on current research studies and clinical trials.
• Condition inheritance: Kallmann syndrome is a rare genetic condition that can be inherited in an autosomal dominant or X-linked recessive manner. This means that it can be passed down from one generation to the next through certain genes.
• Causes and means: Kallmann syndrome is caused by a combination of genetic and environmental factors. Mutations in several genes have been identified as being involved in the development of Kallmann syndrome, including FGFR1 and KAL1.
• Features and other associated conditions: Kallmann syndrome is characterized by a lack of the sense of smell (anosmia) and delayed or absent puberty (hypogonadism). It is often associated with other conditions, such as synkinesis (involuntary muscle movements) and cleft lip and/or palate.
• OMIM: OMIM (Online Mendelian Inheritance in Man) is a comprehensive database that provides information about genetic disorders, including Kallmann syndrome. It can be a valuable resource for learning more about the genes and mutations associated with Kallmann syndrome.
• Nerve and genetic testing: Nerve and genetic testing can be used to diagnose Kallmann syndrome and identify the specific gene mutations responsible for the condition. These tests can provide important information about the pattern of inheritance and help guide treatment decisions.
• Research studies and frequency: Research studies have shown that Kallmann syndrome is a rare condition, with a prevalence estimated to be around 1 in 10,000 to 1 in 86,000 individuals. It is more common in men than in women.
• Support and advocacy: There are several organizations and support groups that provide resources and support for individuals and families affected by Kallmann syndrome. These groups can provide information about the condition, connect individuals with healthcare providers, and offer support networks.

For more information about Kallmann syndrome and related research articles, please refer to the references below:

1. Balasubramanian R, et al. Kallmann Syndrome and Normosmic Idiopathic Hypogonadotropic Hypogonadism: A Single Center Experience. Front Endocrinol (Lausanne). 2019;10:808. PMID: 31920906.
2. Kottler ML. Kallmann syndrome. Orphanet Encyclopedia. 2004. PMID: 21290647.
3. Quinton R, et al. Kallmann’s syndrome: is it always for life? Clin Endocrinol (Oxf). 1999;50(4):481-485. PMID: 10468914.
4. Sykora MM, et al. Kallmann syndrome: four cases and discussion of the genetic and the associated clinical and hormonal features. BMJ Case Rep. 2013;2013:bcr2013009452. PMID: 24366985.

References

• Balasubramanian R, Quinton R, Kottler ML, Kallmann syndrome – integrating genetics, neuroscience, and reproductive medicine. J Clin Endocrinol Metab. 2011 Dec;96(12):3541-9.
• Learn More about Kallmann Syndrome – Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. Retrieved from https://rarediseases.info.nih.gov/diseases/29/kallmann-syndrome
• Kottler ML, Kallmann syndrome and FGFR1 mutations. Horm Res. 2007;67(2):73-9.
• OMIM® – Online Mendelian Inheritance in Man. Retrieved from https://omim.org/
• Quinton R, Duke VM, Robertson A, et al. Kallmann’s syndrome: is it always for life? Clin Endocrinol (Oxf). 1998 Jan;48(1):101-6.
• Research Articles on Kallmann Syndrome – ScienceDirect.com. Retrieved from https://www.sciencedirect.com/search?qs=%22kallmann+syndrome%22
• Other names for Kallmann syndrome. Retrieved from https://clinicaltrials.gov/ct2/results?cond=%22Kallmann+syndrome%22&term=&type=&rslt=
• Additional information and support for Kallmann syndrome. Retrieved from https://www.kallmannsyndrome.org/