دورية أكاديمية
Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome
| العنوان: | Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome |
|---|---|
| المؤلفون: | Prasad, Rathi, Hadjidemetriou, Irene, Maharaj, Avinaash, Meimaridou, Eirini, Buonocore, Federica, Saleem, Moin, Hurcombe, Jenny, Bierzynska, Agnieszka, Barbagelata, Eliana, Bergadá, Ignacio, Ram, Nanik |
| المصدر: | Section of Diabetes, Endocrinology and Metabolism |
| بيانات النشر: | eCommons@AKU |
| سنة النشر: | 2017 |
| المجموعة: | The Aga Khan University: eCommons@AKU |
| مصطلحات موضوعية: | Sphingosine-1-Phosphate Lyase Mutation, Primary Adrenal Insufficiency, Steroid-Resistant Nephrotic Syndrome, Endocrinology, Diabetes, and Metabolism |
| الوصف: | Primary adrenal insufficiency is life threatening and can present alone or in combination with other comorbidities. Here, we have described a primary adrenal insufficiency syndrome and steroid-resistant nephrotic syndrome caused by loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1). SGPL1 executes the final decisive step of the sphingolipid breakdown pathway, mediating the irreversible cleavage of the lipid-signaling molecule sphingosine-1-phosphate (S1P). Mutations in other upstream components of the pathway lead to harmful accumulation of lysosomal sphingolipid species, which are associated with a series of conditions known as the sphingolipidoses. In this work, we have identified 4 different homozygous mutations, c.665G>A (p.R222Q), c.1633_1635delTTC (p.F545del), c.261+1G>A (p.S65Rfs*6), and c.7dupA (p.S3Kfs*11), in 5 families with the condition. In total, 8 patients were investigated, some of whom also manifested other features, including ichthyosis, primary hypothyroidism, neurological symptoms, and cryptorchidism. Sgpl1–/– mice recapitulated the main characteristics of the human disease with abnormal adrenal and renal morphology. Sgpl1–/– mice displayed disrupted adrenocortical zonation and defective expression of steroidogenic enzymes as well as renal histology in keeping with a glomerular phenotype. In summary, we have identified SGPL1 mutations in humans that perhaps represent a distinct multisystemic disorder of sphingolipid metabolism. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://ecommons.aku.edu/pakistan_fhs_mc_med_diabet_endocrinol_metab/27Test; https://www.jci.org/articles/view/90171Test |
| الإتاحة: | https://ecommons.aku.edu/pakistan_fhs_mc_med_diabet_endocrinol_metab/27Test https://www.jci.org/articles/view/90171Test |
| رقم الانضمام: | edsbas.5313D86E |
| قاعدة البيانات: | BASE |
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edsbas BASE edsbas.5313D86E 811 3 Academic Journal academicJournal 810.555480957031 |
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