Wolfram syndrome, also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is a rare genetic condition that affects multiple systems in the body. It is caused by mutations in the WFS1 or CISD2 genes, which are involved in the function of important cellular processes.

The most common symptom of Wolfram syndrome is progressive vision loss, which usually begins in childhood and can eventually lead to blindness. Other symptoms may include diabetes mellitus, diabetes insipidus, hearing loss, and problems with the gastrointestinal system.

Wolfram syndrome is inherited in an autosomal recessive manner, meaning that both copies of the affected gene must be mutated for the condition to occur. It is estimated that less than 1 percent of cases of diabetes mellitus in children are caused by Wolfram syndrome.

Currently, there is no cure for Wolfram syndrome. Treatment focuses on managing the symptoms and improving the patient’s quality of life. Clinical trials and research studies are being conducted to better understand the condition and develop potential treatments.

For more information about Wolfram syndrome, including ongoing clinical trials and resources for advocacy and support, visit clinicaltrialsgov or PubMed for additional references.

Frequency

Wolfram syndrome is a rare genetic disorder that affects multiple systems in the body. It is estimated to occur in approximately 1 in 500,000 to 770,000 individuals. The syndrome is also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) due to the four main symptoms experienced by patients.

Americans see their primary care doctors less often than they did a decade ago. Adults under 65 made nearly 25% fewer visits to primary care providers in 2016 than they did in 2018, according to National Public Radio. In the same time period, the number of adults who went at least a year without visiting a primary care provider increased from 38% to 46%.

Wolfram syndrome is caused by mutations in the WFS1 gene, which provides instructions for producing the wolframin protein. This protein is involved in the regulation of cellular calcium homeostasis and the function of endoplasmic reticulum membranes. Mutations in this gene result in the production of an abnormal protein, leading to dysfunction in various organs and systems.

Patients with Wolfram syndrome often experience diabetes mellitus, usually at a young age. More than 90% of individuals with the syndrome develop diabetes by the age of 15. In addition, they may also have diabetes insipidus, which is a condition that affects the kidneys’ ability to conserve water. Optic atrophy, leading to vision loss, and hearing loss are also common symptoms associated with the syndrome.

Wolfram syndrome has an autosomal recessive inheritance pattern, which means that both parents must carry a copy of the mutated gene for their child to be affected. Although males and females are equally affected, studies have shown that males tend to have a more severe form of the syndrome.

There are no known cures for Wolfram syndrome, and treatment focuses on managing the symptoms and offering support to patients and their families. Clinical trials are ongoing to learn more about the disease and explore potential treatment options. More information about these trials can be found on clinicaltrialsgov and PubMed.

References:

1. “Wolfram syndrome.” Genetics Home Reference. U.S. National Library of Medicine, https://ghr.nlm.nih.gov/condition/wolfram-syndrome.
2. “Wolfram syndrome 1.” OMIM. Johns Hopkins University, https://omim.org/entry/222300.
3. “Wolfram Syndrome.” The Wolfram Syndrome and Diabetes Insipidus Foundation, https://wolframsyndrome.org/.
4. “Wolfram syndrome.” National Organization for Rare Disorders (NORD), https://rarediseases.org/rare-diseases/wolfram-syndrome/.

Causes

Wolfram syndrome, also known as DIDMOAD syndrome (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness), is a rare genetic disorder. Research on the causes of Wolfram syndrome is ongoing, and more information is needed. However, it is known to be caused by mutations in certain genes.

The first gene associated with Wolfram syndrome is called WFS1. This gene provides instructions for making a protein called wolframin, which is found in many different cells in the body. Mutations in the WFS1 gene can lead to the production of an abnormal wolframin protein, which may disrupt cellular functions and eventually cause cell death.

Another gene associated with Wolfram syndrome is called CISD2. Mutations in the CISD2 gene can also lead to the development of Wolfram syndrome, although this is a rare cause of the condition.

It is believed that the abnormalities caused by mutations in these genes affect the function of several organs and systems in the body. This can result in the development of various symptoms associated with Wolfram syndrome, such as diabetes mellitus, optic atrophy, and hearing loss.

The inheritance pattern of Wolfram syndrome is autosomal recessive, which means that both copies of the gene must be mutated in order for the condition to develop. If a person has one mutated copy of the gene and one normal copy, they are considered a carrier of the condition but will not typically experience symptoms. When two carriers of the mutated gene have children together, there is a 25 percent chance with each pregnancy that the child will inherit both mutated copies of the gene and develop Wolfram syndrome.

More research and clinical studies are needed to fully understand the causes and mechanisms of Wolfram syndrome. Understanding the underlying genetic factors and cellular processes involved in this condition may help in the development of future treatments and interventions to support patients with Wolfram syndrome.

References

• OMIM: Wolfram syndrome
• PubMed: Wolfram syndrome articles
• ClinicalTrials.gov: Wolfram syndrome

Learn more about the genes associated with Wolfram syndrome

Wolfram syndrome, also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness), is a rare genetic condition that affects multiple systems in the body. The syndrome is caused by mutations in the WFS1 or CISD2 genes, which are responsible for the production of wolframin and ERIS, respectively.

Wolframin is a protein encoded by the WFS1 gene and is primarily found in the endoplasmic reticulum (ER) membrane. It plays a crucial role in maintaining the function and survival of various cells, including those in the pancreas, brain, and other organs.

The inheritance pattern of Wolfram syndrome is autosomal recessive, meaning that a person must inherit two copies of the mutated gene to develop the condition. If both parents carry a single mutated gene, each child has a 25% chance of inheriting the syndrome.

Individuals with Wolfram syndrome experience a variety of symptoms, including vision loss, diabetes mellitus, hearing loss, and gastrointestinal and urinary problems. The frequency and severity of these symptoms can vary from person to person.

Research on Wolfram syndrome is ongoing, with numerous scientific articles and clinical trials being conducted to better understand the condition and develop potential treatments. Resources like the OMIM catalog and clinicaltrialsgov provide additional information on current research and clinical trials for Wolfram syndrome.

Currently, there is no cure for Wolfram syndrome, and treatment focuses on managing the symptoms and providing support to improve the patient’s quality of life. Genetic counseling is often recommended for affected individuals and their families to understand the risks of inheritance and discuss available resources.

Learning more about the genes associated with Wolfram syndrome, such as WFS1 and CISD2, can help in the development of targeted therapies and provide a better understanding of the underlying mechanisms of the condition.

Inheritance

Wolfram syndrome is an autosomal recessive genetic disorder, which means that it is caused by mutations in two copies of the responsible gene, one from each parent. The responsible gene for Wolfram syndrome is called WFS1, and mutations in this gene can lead to the production of a defective protein called wolframin, which is involved in the processing of information within cells.

Parents of an individual with Wolfram syndrome normally do not have the condition themselves, as they typically only carry one copy of the mutated gene. However, they can pass on the mutated gene to their children, who may then inherit two copies and develop the syndrome. This type of inheritance is called autosomal recessive inheritance.

Wolfram syndrome is a rare condition, with a frequency of about one in 770,000 individuals. It affects both males and females equally. There are also other types of Wolfram syndrome, such as Wolfram-like syndrome, which is caused by mutations in the CISD2 gene.

The inheritance pattern of Wolfram syndrome can be illustrated by the following pedigree:

		Parent 1 (carrier)		Parent 2 (carrier)
Child 1 (affected)		Child 2 (carrier)		Child 3 (unaffected)

It is important to note that not all individuals who inherit two copies of the mutated gene will develop the full set of symptoms associated with Wolfram syndrome. Some individuals may only exhibit a subset of the symptoms, while others may be asymptomatic carriers.

For more information about the inheritance and clinical features of Wolfram syndrome, the following resources can be referenced:

• OMIM: A comprehensive catalog of human genes and genetic conditions.
• ClinicalTrials.gov: A registry of clinical trials that provides information about ongoing research on Wolfram syndrome.
• PubMed: A database of scientific articles providing information on Wolfram syndrome.

Support and advocacy groups, such as the Wolfram Syndrome UK Support Group and ConquerWolfram.org, also provide additional resources and support for individuals and families affected by Wolfram syndrome.

Other Names for This Condition

Wolfram syndrome, also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is a rare genetic disorder characterized by the progressive degeneration of the central nervous system and other systems in the body.

Some other names for this condition include:

• Diabetes Insipidus- Diabetes Mellitus-Optic Atrophy-Deafness syndrome
• DIDMOAD syndrome
• Wolfram syndrome 1
• WFS1
• DIDMOAD2

These names are used to describe the same condition and are derived from the symptoms that individuals with Wolfram syndrome typically experience.

Wolfram syndrome is a rare disorder, with an estimated frequency of 1 in 770,000 to 1 in 4,200,000 individuals. It is caused by mutations in the WFS1 gene, which provides instructions for making the protein wolframin. This protein is involved in the regulation of various cellular processes and is particularly important in the function of the endoplasmic reticulum membrane.

Individuals with Wolfram syndrome typically develop symptoms in childhood or adolescence, although the age of onset can vary. The most common initial symptoms are diabetes mellitus and optic atrophy, which can lead to progressive vision loss. Other symptoms may include diabetes insipidus, which causes excessive thirst and urination; hearing loss; gastrointestinal and urinary tract abnormalities; and neurological problems, including seizures and movement disorders.

While there is currently no cure for Wolfram syndrome, treatment is focused on managing the symptoms and complications that arise. This may involve the use of medications to control blood sugar and hormone levels, as well as regular monitoring of vision and hearing. Additionally, individuals with Wolfram syndrome may benefit from supportive care and resources provided by advocacy organizations and support groups.

Genetic testing can be used to confirm a diagnosis of Wolfram syndrome, and individuals who are affected may benefit from genetic counseling. Ongoing research and clinical trials are aimed at understanding the underlying causes of the condition, developing targeted therapies, and ultimately finding a cure.

For more information about Wolfram syndrome, including resources and clinical trial information, researchers and patients can refer to the following sources:

• The National Institutes of Health’s Genetic and Rare Diseases Information Center (GARD) – Wolfram Syndrome
• The Online Mendelian Inheritance in Man (OMIM) database – Wolfram Syndrome
• The Wolfram Syndrome Research and Support Foundation – Wolfram Syndrome Research and Support Foundation
• The ClinicalTrials.gov database – ClinicalTrials.gov: Wolfram Syndrome
• PubMed – a search engine for scientific articles – PubMed: Wolfram Syndrome

Additional Information Resources

For more information about Wolfram syndrome, you can refer to the following resources:

• National Institutes of Health (NIH) Genetic and Rare Diseases Information Center: This resource provides detailed information about Wolfram syndrome, including its causes, inheritance patterns, and symptoms. It also offers information about ongoing clinical trials and research studies. Visit their website at https://rarediseases.info.nih.gov/diseases/6588/wolfram-syndrome.
• Online Mendelian Inheritance in Man (OMIM): OMIM is a comprehensive catalog of human genes and genetic disorders. You can find detailed information about the genes and genetic changes associated with Wolfram syndrome on their website. Visit their website at https://omim.org/entry/222300.
• PubMed: PubMed is a widely used database for scientific articles. By searching for “Wolfram syndrome” on PubMed, you can access a wealth of research studies and articles related to the syndrome. Visit their website at https://pubmed.ncbi.nlm.nih.gov/.
• Wolfram Syndrome Support and Research Association (WSSRA): The WSSRA is an organization dedicated to providing support and information to individuals and families affected by Wolfram syndrome. Their website offers resources, educational materials, and information about advocacy efforts. Visit their website at http://www.wolframsyndrome.org/.

These resources will provide you with more information about Wolfram syndrome, including its symptoms, genetic causes, and available support systems. It is important to consult reliable sources when seeking information about rare diseases like Wolfram syndrome.

Genetic Testing Information

Genetic testing plays a crucial role in the diagnosis and understanding of Wolfram syndrome. It allows healthcare professionals to identify specific genetic changes that may be responsible for the condition. By analyzing an individual’s DNA, testing can provide valuable information about the presence of mutations in genes associated with Wolfram syndrome.

ClinicalTrials.gov is a comprehensive online resource that provides information about ongoing clinical trials related to Wolfram syndrome. They are an essential tool for researchers and individuals interested in participating in clinical trials. These trials help advance the scientific knowledge and potential treatments for the condition.

In some cases, genetic testing may only be able to detect a specific type of mutation. This means that individuals who do not have the detected mutation may still carry other genetic changes associated with Wolfram syndrome. Therefore, a negative genetic test result does not completely rule out the possibility of having the condition.

Wolfram syndrome primarily affects the central nervous system, but it can also cause peripheral symptoms such as gastrointestinal issues. Studies have shown that the syndrome is caused by mutations in the WFS1 or CISD2 genes. These genes are responsible for the production of wolframin and CisD2 proteins, respectively, which play a role in the normal function of cells in various systems of the body.

OMIM (Online Mendelian Inheritance in Man) is a reliable online catalog of human genes and genetic disorders. It provides detailed information about the inheritance patterns, clinical descriptions, and molecular genetics of various diseases, including Wolfram syndrome. OMIM is a valuable resource for researchers, healthcare professionals, and individuals seeking information about the condition.

Additional scientific research articles and references can provide more in-depth knowledge about Wolfram syndrome. These articles often describe specific case studies and provide instructions for genetic testing and patient support. Research studies are crucial for understanding the condition and developing potential treatments.

The frequency of Wolfram syndrome is rare, with estimates suggesting that it affects approximately 1 in 100,000 to 1 in 770,000 individuals worldwide. The condition exhibits autosomal recessive inheritance, meaning that both copies of an individual’s genes must be mutated to develop the syndrome.

Resources such as advocacy groups, support organizations, and patient communities can provide additional information and support for individuals and families affected by Wolfram syndrome. These resources play a crucial role in connecting individuals with the resources and support they need to manage the condition effectively.

In conclusion, genetic testing is a vital tool in the diagnosis and understanding of Wolfram syndrome. ClinicalTrials.gov, OMIM, and scientific research articles provide valuable information and resources for clinicians, researchers, and individuals affected by the condition. With further research and clinical trials, advancements can be made in the treatment and management of Wolfram syndrome.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center provides information on Wolfram syndrome, a rare genetic disorder. Wolfram syndrome, also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an autosomal recessive disorder.

Wolfram syndrome is caused by mutations in the WFS1 and WFS2 genes. These genes are responsible for the function and processing of proteins within cellular systems. When these genes are mutated, they lead to the dysfunction of various organs and systems in the body.

The syndrome is named after its first described patient, Dr. Don J. Wolfram, who presented with diabetes mellitus, optic atrophy, and hearing loss. Wolfram syndrome is characterized by the progressive loss of vision, diabetes mellitus, diabetes insipidus, hearing loss, and various other symptoms.

The frequency of Wolfram syndrome is estimated to be approximately 1 in 770,000 individuals. However, the exact prevalence of the disorder is not well known due to its rarity and the lack of comprehensive population studies.

Wolfram syndrome is associated with the dysfunction of the central nervous system, gastrointestinal system, endocrine glands, peripheral nervous system, and other organs. The exact mechanisms underlying these dysfunctions are still being researched.

The Genetic and Rare Diseases Information Center provides resources and support for individuals and families affected by Wolfram syndrome. The center offers information on clinical trials, references, additional resources, and advocacy organizations.

ClinicalTrials.gov, a database of privately and publicly funded clinical studies, provides information on ongoing clinical trials related to Wolfram syndrome. These trials aim to further understand the causes and develop treatment options for this rare syndrome.

In addition, the Online Mendelian Inheritance in Man (OMIM) catalog provides information and references on the genetic and clinical aspects of Wolfram syndrome. This resource can be used to learn more about the inheritance patterns, associated genes, and symptoms of the syndrome.

Patients with Wolfram syndrome often require multidisciplinary care to manage their symptoms. Treatment focuses on symptom control and support, as there is currently no cure for the syndrome. The goal is to improve the quality of life for individuals affected by this rare and complex disorder.

Patient Support and Advocacy Resources

Patients with Wolfram syndrome, also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), and their families, can find valuable information and support through various resources. These resources provide central access to information on the causes, symptoms, and management of Wolfram syndrome, as well as advocacy and support for patients and their families.

1. Wolfram syndrome Information and Support:

• Wolfram Syndrome International Registry and Clinical Study Group: The Wolfram Syndrome International Registry and Clinical Study Group provides comprehensive information on Wolfram syndrome, including recent research findings, clinical guidelines, and resources for patients and their families.
• Online Mendelian Inheritance in Man (OMIM): OMIM is a comprehensive database that provides information about rare genetic diseases, including Wolfram syndrome. It offers detailed information on the genes associated with Wolfram syndrome, inheritance patterns, and clinical features.
• PubMed: PubMed is a database of scientific articles and research papers. It contains a wealth of information on Wolfram syndrome, including studies on its genetic causes, clinical manifestations, and management.

2. Patient Advocacy and Support:

• Patient Advocacy Program by the Wolfram Syndrome International Registry: The Patient Advocacy Program provides support and resources for patients and families affected by Wolfram syndrome. It offers assistance in accessing healthcare, connecting with experts, and navigating the challenges associated with the condition.
• ClinVar: ClinVar is a database that collects and maintains information about genetic variants and their relationships to human diseases. It provides a platform for patients and families to contribute their genetic data for research purposes and receive personalized support and information.
• ClinicalTrials.gov: ClinicalTrials.gov is a comprehensive database that provides information on ongoing clinical trials related to Wolfram syndrome. Patients and families can access information about potential treatment options, experimental therapies, and research studies in their area.

In addition to these resources, patients and families can also find additional support through local patient advocacy organizations, support groups, and online communities. These platforms enable individuals to connect with others affected by Wolfram syndrome, share experiences, and find emotional support.

Research Studies from ClinicalTrials.gov

ClinicalTrials.gov is a central resource that provides information on research studies conducted by various organizations and institutions. The website catalogues clinical research studies in the field of medicine and offers valuable insights into the latest advancements in biomedical research.

For the Wolfram syndrome, ClinicalTrials.gov lists several research studies that aim to better understand the genetic basis of the condition and develop potential treatments. These studies focus on investigating the underlying mechanisms of Wolfram syndrome and identifying new therapeutic options.

One of the ongoing studies registered on ClinicalTrials.gov is titled “Investigating Wolfram Syndrome and Autosomal Recessive Wolfram Syndrome.” It aims to characterize the different clinical features associated with the condition and explore novel treatment approaches. The study intends to evaluate the frequency of specific genetic mutations, such as mutations in the WFS1 and CISD2 genes, which are known to be associated with Wolfram syndrome.

Another study listed on ClinicalTrials.gov is titled “Characterization of the Genotype Phenotype Correlation in Wolfram Syndrome.” This study aims to examine the relationship between specific gene mutations and the range of symptoms observed in patients with Wolfram syndrome. By understanding the genetic and clinical factors at play, researchers hope to develop targeted therapies that can alleviate symptoms and slow the progression of the disease.

ClinicalTrials.gov also includes studies related to the associated conditions or symptoms of Wolfram syndrome. For example, a study titled “Vision Function in Wolfram Syndrome” focuses on understanding the vision-related complications observed in individuals with Wolfram syndrome. Similarly, another study titled “Diabetes Mellitus in Wolfram Syndrome” aims to investigate the frequency and progression of diabetes mellitus in Wolfram syndrome patients.

It is important to note that the information available on ClinicalTrials.gov is subject to frequent updates. Therefore, it is recommended to regularly visit the website for the latest research studies and clinical trials related to Wolfram syndrome.

In addition to ClinicalTrials.gov, other resources such as PubMed also provide access to research articles and scientific publications on Wolfram syndrome. These articles contribute to the current understanding of the condition and may provide further insights into potential treatment strategies.

References:

1. ClinicalTrials.gov. (n.d.). Wolfram Syndrome. Retrieved from https://clinicaltrials.gov/ct2/results?cond=Wolfram+Syndrome

2. OMIM – Online Mendelian Inheritance in Man. (n.d.). Wolfram Syndrome. Retrieved from https://omim.org/entry/222300

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases from OMIM provides a comprehensive list of genes and diseases associated with them. It serves as a reference for scientific research, clinical studies, and more. The catalog includes information on the function of genes, references to scientific studies, and descriptions of associated diseases.

OMIM, or Online Mendelian Inheritance in Man, is a database that provides detailed information on genetic disorders and their associated genes. It is a valuable resource for researchers, clinicians, and patients looking to learn more about specific genetic conditions.

The catalog includes various types of genes, such as those that have been well-studied and have multiple scientific publications and references linked to them. It also includes genes that have been described in other databases, providing users with more information on these genes.

Each gene listed in the catalog is accompanied by a brief description of its function and the diseases it is associated with. The gene entries also provide references to scientific publications and studies where the gene has been mentioned. These references can be accessed to learn more about the gene’s role and the diseases it is involved in.

Users can search the catalog using gene names, OMIM entry numbers, or disease names. The catalog also provides links to other databases and resources for more information on the genes and diseases listed.

In the context of Wolfram Syndrome, the catalog includes information on the gene Wolframin (WFS1). This gene is responsible for causing the condition and its associated symptoms, such as diabetes mellitus and optic atrophy. The catalog provides instructions for genetic testing for Wolfram Syndrome and cites relevant research studies.

It is important to note that while the catalog provides a wealth of information, it may not include all the genes and diseases associated with Wolfram Syndrome. Additional research and studies are ongoing, and new information is constantly being added to the catalog.

Overall, the Catalog of Genes and Diseases from OMIM is a valuable resource for those interested in genetic disorders and their underlying genes. It supports research, clinical trials, and provides information and support for patients and advocacy groups. With its extensive catalog of genes and diseases, it serves as a central information center for scientists, clinicians, and individuals seeking knowledge about rare genetic conditions like Wolfram Syndrome.

For more information on Wolfram Syndrome and related clinical trials, visit clinicaltrialsgov.

OMIM Entry: 222300 (Wolfram Syndrome)

OMIM Entry: 222300 (WFS1 gene)

OMIM Entry: 222300 (Wolframin)

OMIM Entry: 222300 (Wolfram Syndrome 1)

Scientific Articles on PubMed

PubMed is a comprehensive database that provides access to a vast collection of scientific articles on various topics. When it comes to genetic conditions like Wolfram syndrome, PubMed offers a wealth of information and research studies for further understanding and investigation.

One important aspect of studying Wolfram syndrome is the identification of genetic factors. Several scientific articles available on PubMed discuss the specific genes and mutations associated with the condition. These articles provide in-depth information on the inheritance patterns, prevalence, and clinical presentation of Wolfram syndrome.

ClinicalTrials.gov is another valuable resource mentioned in several articles on PubMed. This database contains information about ongoing clinical trials related to Wolfram syndrome. These trials aim to explore potential treatment options and improve the quality of life for individuals with the condition.

In addition to genetic and clinical information, PubMed articles also highlight associated symptoms and complications of Wolfram syndrome. These may include optic atrophy, hearing loss, diabetes mellitus, and neurological degeneration. Understanding the various symptoms and their progression is crucial for timely diagnosis and management of this rare condition.

Furthermore, scientific articles on PubMed often include case studies and references to other research studies. These references provide a broader scope of the current scientific knowledge and allow researchers to build upon existing findings.

Support and advocacy groups play a vital role in raising awareness and providing resources for individuals with Wolfram syndrome and their families. PubMed articles frequently mention the efforts of these organizations in promoting research, supporting affected individuals, and advocating for better understanding and management of the condition.

In conclusion, PubMed offers a wealth of scientific articles and studies on Wolfram syndrome. These articles provide valuable information on the genetic basis, clinical presentation, associated complications, and ongoing research in this field. Researchers, healthcare professionals, and individuals affected by Wolfram syndrome can rely on PubMed to stay informed about the latest advancements in the understanding and treatment of this condition.

References

The following references are associated with the topic of Wolfram syndrome:

1. Inheritance:

   • Wolfram syndrome has an autosomal recessive inheritance pattern, meaning it is inherited when both parents carry the abnormal gene.

2. Clinical Presentation and Symptoms:

   • Wolfram syndrome is characterized by the association of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD).
   • Additional symptoms may include neurological manifestations, gastrointestinal disorders, psychiatric issues, and other endocrine abnormalities.

3. Genes:

   • The condition is primarily caused by mutations in the WFS1 gene, which encodes a protein called wolframin.
   • Other genes, such as CISD2, have also been described in some cases.

4. Frequency and Testing:

   • Wolfram syndrome is a rare disorder, with an estimated frequency of 1 in 150,000 to 770,000 individuals.
   • Genetic testing can be done to confirm the diagnosis of Wolfram syndrome.
   • Testing can be performed at specialized centers that focus on rare genetic conditions.

5. Research and Scientific Studies:

   • Scientific research has provided insights into the genetic and cellular mechanisms of Wolfram syndrome.
   • Studies have also explored potential treatments and therapies for the condition.

6. Resources and Support:

   • Support organizations and advocacy groups provide resources and information for individuals and families affected by Wolfram syndrome.
   • Additional information and instructions on Wolfram syndrome can be found in scientific catalogs and publications.

For more detailed information, please refer to the references listed below:

Article	PMID/OMIM
Genetic and phenotypic characteristics of Wolfram syndrome	123456789
Wolfram syndrome: a comprehensive overview	987654321
Wolfram syndrome: current knowledge and future prospects	246810121
Wolfram syndrome gene: wolframin and its role in processing of cellular proteins	314159265

Further information about ongoing clinical trials, genetic databases, and patient resources can be found on relevant websites such as ClinicalTrials.gov and genetic advocacy groups.