dc.contributor.author | Maharaj, A | |
dc.contributor.author | Theodorou, D | |
dc.contributor.author | Banerjee, II | |
dc.contributor.author | Metherell, LA | |
dc.contributor.author | Prasad, R | |
dc.contributor.author | Wallace, D | |
dc.date.accessioned | 2020-04-30T14:49:46Z | |
dc.date.available | 2020-03-18 | |
dc.date.available | 2020-04-30T14:49:46Z | |
dc.date.issued | 2020-04-08 | |
dc.identifier.citation | Maharaj A, Theodorou D, Banerjee I, Metherell LA, Prasad R and Wallace D (2020) A Sphingosine-1-Phosphate Lyase Mutation Associated With Congenital Nephrotic Syndrome and Multiple Endocrinopathy. Front. Pediatr. 8:151. doi: 10.3389/fped.2020.00151 | en_US |
dc.identifier.issn | 2296-2360 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/63870 | |
dc.description.abstract | Background: Loss of function mutations in SGPL1 are associated with Sphingosine-1-phosphate lyase insufficiency syndrome, comprising steroid resistant nephrotic syndrome, and primary adrenal insufficiency (PAI) in the majority of cases. SGPL1 encodes sphingosine-1-phosphate lyase (SGPL1) which is a major modulator of sphingolipid signaling. Case Presentation: A Pakistani male infant presented at 5 months of age with failure to thrive, nephrotic syndrome, primary adrenal insufficiency, hypothyroidism, and hypogonadism. Other systemic manifestations included persistent lymphopenia, ichthyosis, and motor developmental delay. Aged 9 months, he progressed rapidly into end stage oligo-anuric renal failure and subsequently died. Sanger sequencing of the entire coding region of SGPL1 revealed the novel association of a rare homozygous mutation (chr10:72619152, c.511A>G, p.N171D; MAF-1.701e-05) with the condition. Protein expression of the p.N171D mutant was markedly reduced compared to SGPL1 wild type when overexpressed in an SGPL1 knockout cell line, and associated with a severe clinical phenotype. Conclusions: The case further highlights the emerging phenotype of patients with loss-of-function SGPL1 mutations. Whilst nephrotic syndrome is a recognized feature of other disorders of sphingolipid metabolism, sphingosine-1-phosphate lyase insufficiency syndrome is unique amongst the sphingolipidoses in presenting with multiple endocrinopathies. Given the multi-systemic and progressive nature of this form of PAI/ nephrotic syndrome, a genetic diagnosis is crucial for optimal management and appropriate screening for comorbidities in these patients. | en_US |
dc.format.extent | 151 | |
dc.language | eng | |
dc.publisher | Frontiers Media | en_US |
dc.relation.ispartof | Front Pediatr | |
dc.rights | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | |
dc.subject | SGPL1 | en_US |
dc.subject | congenital nephrotic syndrome | en_US |
dc.subject | multiple endocrinopathy | en_US |
dc.subject | primary adrenal insufficiency | en_US |
dc.subject | sphingosine-1-phosphate lyase | en_US |
dc.title | A Sphingosine-1-Phosphate Lyase Mutation Associated With Congenital Nephrotic Syndrome and Multiple Endocrinopathy. | en_US |
dc.type | Article | en_US |
dc.rights.holder | © 2020 Maharaj, Theodorou, Banerjee, Metherell, Prasad and Wallace. | |
dc.identifier.doi | 10.3389/fped.2020.00151 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/32322566 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.publisher-url | https://doi.org/10.3389/fped.2020.00151 | |
pubs.volume | 8 | en_US |
dcterms.dateAccepted | 2020-03-18 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
qmul.funder | Investigating the role of the sphingolipid pathway in a novel syndromic form of primary adrenal insufficiency::Barts Charity | en_US |
qmul.funder | Investigating the role of the sphingolipid pathway in a novel syndromic form of primary adrenal insufficiency::Barts Charity | en_US |