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{
"titles": [
"2017 - Spectrum of mutations in monogenic diabetes genes identified from high-throughput DNA sequencing of 6888 individuals.pdf",
"1995 - Neurodegeneration and diabetes UK nationwide study of Wolfram syndrome.pdf",
"2008 - Learning From Molecular Genetics.pdf",
"2021 - Monogenic diabetes a gateway to precision medicine.pdf",
"1995 - Neurodegeneration and diabetes UK nationwide study of Wolfram syndrome.pdf",
"1995 - Neurodegeneration and diabetes UK nationwide study of Wolfram syndrome.pdf",
"2021 - Monogenic diabetes a gateway to precision medicine.pdf",
"2021 - Monogenic diabetes a gateway to precision medicine.pdf",
"2010 - Family History of Diabetes and Prevalence.pdf",
"2017 - Spectrum of mutations in monogenic diabetes genes identified from high-throughput DNA sequencing of 6888 individuals.pdf"
],
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"WFS1 and genotype-phenotype correlation in Wolfram syndrome. Am J Med Genet A. 2007;143A(14):1605 12. 61. McCarthy MI. Painting a new picture of personalised medicine for diabetes. Diabetologia. 2017;60(5):793 9. 62. Fuchsberger C, Flannick J, Teslovich TM, et al. The genetic architecture of type 2 diabetes. Nature. 2016;536(7614):41 7. 63. Patch AM, Flanagan SE, Boustred C, Hattersley AT, Ellard S. Mutations in the ABCC8 gene encoding the SUR1 subunit of the KATP channel cause",
"enable physicians to ameliorate some of the complications that so devastate the lives of these patients. Three questions need answers from further studies: is there really a lack of diabetic complications in Wolfram syndrome patients compared with other diabetics? What is the nature of the neurodegeneration and its relation to diabetes mellitus? Are heterozygotes for Wolfram syndrome at risk of maturity-onset diabetes? This paper is dedicated to the memory of Robin Smith, a Wolfram",
"Monogenic and syndromic forms account for only a small,though highly informative, proportion of cases of nonau-toimmune diabetes. The challenge for medical science liesin bringing equivalent mechanistic insights and transla-tional benets to the hundreds of millions of peoplealready affected by, or at risk of, more common, typicalforms of diabetes. For type 2 diabetes, there is abundantevidence that individual susceptibility is inuenced byboth the combination of genetic variation at multiple sitesand a",
"responding to two causative genes have been identified to date. Wolfram syndrome 1 (WS1), characterized by diabetes insipidus, DM, optic atrophy, and deafness, is a rare autosomal recessive disease caused by variants in wolframin ER transmembrane gly- coprotein (WFS1). Severe cases with dominant heterozygous vari- ants are also reported (92). Often, patients first manifestation is DM at an average age of 6 years. Though most WS1 patients",
"finding study to describe the natural history, complications, prevalence, and inheritance of the syndrome. We identified 45 patients with Wolfram syndrome—a prevalence of one per 770000. Non-autoimmune, insulin- deficient diabetes mellitus presented at a median age of 6 years, followed by optic atrophy (11 years). Cranial diabetes insipidus occurred in 33 patients (73%) with sensorineural deafness (28, 62%) in the second decade; renal-tract abnormalities (26, 58%) presented in the third",
"Wolfram patients have a mitochondrial genome abnormality, but this has not yet been shown. The differential diagnosis indicates the importance of accurate clinical descriptions when presenting cases of the syndrome. Our study has implications for basic science and practice: more accurate characterisation of the syndrome will allow assessment of genotype/phenotype correlations; and earlier recognition of diabetes insipidus, gastrointestinal dysfunction, and central apnoeas should",
"onset diabetes of the young, multiple causes of neonatal DM, and syndromic diabetes such as Wolfram syndrome and lipodystrophy. We also review methods of prioritizing patients undergoing genetic testing, and highlight existing challenges facing sequence data interpretation that can be addressed by forming collaborations of expertise and by pooling cases.Monogenic diabetes: a gateway to precision medicine in diabetes Haichen Zhang,1 Kevin Colclough,2 Anna L. Gloyn,3,4 and Toni I. Pollin1",
"WFS1 mutations underlie a genetic syndrome of neonatal/infancy-onset diabetes, congenital sensorineural deafness, and congenital cataracts. Diabetes . 2017;66(7):20442053. 93. Rigoli L, Di Bella C. Wolfram syndrome 1 and Wolfram syndrome 2. Curr Opin Pediatr. 2012;24(4):512517 . 94. Bansal V, et al. Identification of a missense vari- ant in the WFS1 gene that causes a mild form of Wolfram syndrome and is associated with risk for type 2 diabetes in Ashkenazi Jewish individuals.",
"established. It has been corroborated by a series of obser-vations that include ethnic differences, familial aggrega-tion, twin studies, admixture studies, linkage studies, monogenic cases (e.g., MODY), mitochondrial cases of diabetes, and a constantly growing number of molecular markers [5] . On the other hand, the genetics of the meta- bolic syndrome remains complex [6] . It is highly unlikely that a single gene will account for a substantial portion",
"diabetes (0.5% carrier frequency) compared to controls (0.035%). One individual with early onset diabetes was homozygous for a rare pathogenic missense variant in the WFS1 gene but did not have the additional phenotypes associated with Wolfram syndrome. Conclusion: Targeted sequencing of genes linked with monogenic diabetes can identify disease-relevant mutations in individuals diagnosed with type 2 diabetes not suspected of having monogenic forms of the disease. Our data suggests"
],
"answer": "Studying the genetic basis of syndromic forms of diabetes, such as Wolfram Syndrome, has provided several insights: 1. **Genotype-Phenotype Correlation**: Research has highlighted the importance of understanding genotype-phenotype correlations in Wolfram Syndrome. This involves identifying specific genetic mutations and understanding how they manifest in clinical symptoms, which can aid in more accurate diagnosis and management of the syndrome [1], [6]. 2. **Genetic Mutations**: Wolfram Syndrome is primarily caused by mutations in the WFS1 gene, which encodes the wolframin ER transmembrane glycoprotein. These mutations lead to a range of symptoms including diabetes mellitus, optic atrophy, and deafness. Some severe cases are associated with dominant heterozygous variants [4]. 3. **Early Onset and Symptoms**: The syndrome is characterized by early onset of diabetes mellitus, typically around the age of 6, followed by other symptoms such as optic atrophy and sensorineural deafness in later years [5]. 4. **Potential for Broader Implications**: Insights from studying Wolfram Syndrome have implications for basic science and clinical practice. They emphasize the need for accurate clinical descriptions and early recognition of symptoms, which can improve patient outcomes and inform treatment strategies [6]. 5. **Risk Assessment**: There is ongoing research to determine if heterozygotes for Wolfram Syndrome are at risk for maturity-onset diabetes, which could have implications for understanding genetic risk factors in broader populations [2]. These insights not only enhance our understanding of Wolfram Syndrome but also contribute to the broader field of genetic research in diabetes, potentially informing personalized medicine approaches for more common forms of the disease.",
"question": "What insights have been gained from studying the genetic basis of syndromic forms of diabetes, such as Wolfram Syndrome and Alstr\u00f6m Syndrome?"
}
|
