Genotype and phenotype variability in Sjögren-Larsson syndrome

Weustenfeld, Maximilian; Eidelpes, Reiner; Schmuth, Matthias; Rizzo, William B.; Zschocke, Johannes; Keller, Markus A.

doi:10.1002/humu.23679

Cited by 25 publications

(31 citation statements)

References 76 publications

(105 reference statements)

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“…Aldh3a2 can code fatty aldehyde dehydrogenase in mammal, 34,35 and pathogenic variants of Aldh3a2 lead to Sjögren-Larsson syndrome. 36 Herein, we confirmed that TOE exhibited a promoting effect on the fatty acid degradation by increasing Acox3, Adh5 and Aldh3a2 expression in DSS-induced colitis.…”

Section: Discussionsupporting

confidence: 69%

Taraxacum officinale extract ameliorates dextran sodium sulphate‐induced colitis by regulating fatty acid degradation and microbial dysbiosis

Chen

Fan

Liang

et al. 2019

J Cellular Molecular Medi

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Numerous data show that taraxacum officinale extract (TOE) exerts protective effects on inflammatory diseases. However, the underlying mechanisms by which TOE affects dextran sulphate sodium (DSS)‐induced colitis remain unclear. After DSS‐induced colitis were treated with different concentrations of TOE for 8 days, the bodyweight, disease activity index (DAI), colon lengths and pathological scoring were assessed, and histopathological examination was confirmed by HE staining. Furthermore, a transcriptome sequencing was performed by using the colon tissues between TOE and DSS groups, and the differentially expressed genes were conducted for the Kyoto Encyclopaedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) and were validated by qRT‐PCR and immunohistochemistry analysis. In addition, a 16S rDNA sequencing was carried out to distinguish the differential gut microbiota by using the mouse faecal samples between TOE and DSS groups. We found that TOE attenuated the clinical symptoms, lowered the inflammatory scoring and inhibited the secretion of proinflammatory factors TNF‐α, IL‐1β and IL‐6 in DSS‐induced colitis. KEGG and GSEA analysis demonstrated that fatty acid degradation and cytokine‐receptor signalling were predominantly enriched in TOE‐treated colitis as compared with the DSS group. Further investigations revealed that TOE increased the expression levels of Adh5, Aldh3a2 and Acox3, but decreased those of CCL20, CCR6 and CXCL1/5 in DSS‐induced colitis, where TOE also induced the enrichment of S24‐7 and adlercreutzia, but decreased the amount of anaerostipes, enterococcus, enterobacteriaceae and peptostreptococcaceae. In conclusion, TOE ameliorated DSS‐induced colitis by regulating fatty acid degradation and microbial dysbiosis.

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Section: Discussionsupporting

confidence: 69%

Taraxacum officinale extract ameliorates dextran sodium sulphate‐induced colitis by regulating fatty acid degradation and microbial dysbiosis

Chen

Fan

Liang

et al. 2019

J Cellular Molecular Medi

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“…Isolated or infrequent seizures occur in 35-40% of the patients. 3,7 Seizures are usually generalized tonic-clonic in type. They are not a prominent feature and usually controlled with anti-epileptic agents.…”

Section: Seizuresmentioning

confidence: 99%

“…Recently, the phenotypic data of the SLS patients was merged into a concise genotype based open-access database (www.LOVD.nl/ALDH3A2). 7 There were 178 patients identified in the database with 90 unique SLS causing variants. The mutations include amino acid substitutions/deletions/ insertions, splicing defects and complex rearrangements.…”

Section: Ophthalmologic Findingsmentioning

confidence: 99%

“…3 However, it has been described worldwide. [4][5][6][7] Diagnosis requires measurement of FALDH activity in cultured fibroblasts or mutation analysis of the FALDH gene. Deficiency of fatty acid aldehyde dehydrogenase (FALDH) causes an accumulation of fatty alcohols and fatty aldehydes, leading to altered cell-membrane integrity primarily affecting skin, eyes, and the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

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<p>Sjogren-Larsson Syndrome: Mechanisms and Management</p>

Sankaran¹

2020

TACG

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Sjogren Larsson syndrome (SLS) is a rare autosomal recessive inborn error of lipid metabolism due to mutations in the ALDH3A2 that result in a deficiency of fatty aldehyde dehydrogenase (FALDH). The syndrome has a high prevalence in Sweden where it was first described, but now known to occur worldwide. The classical triad of ichthyosis, mental retardation and spasticity characterizes clinical features. Preterm birth is common. "Glistening white dots" in the retina is a pathognomic clinical feature. Magnetic resonance imaging of the brain demonstrates leukoencephalopathy predominant in the periventricular region. Cerebral MR spectroscopy reveals a characteristic abnormal lipid peak at 1.3ppm and a small peak at 0.9ppm. The primary role of FALDH is oxidation of medium and long-chain aliphatic aldehydes derived from fatty alcohol, phytanic acid, ether glycerolipids and sphingolipids. The diagnosis is based on the typical phenotype, demonstration of the enzyme deficiency and presence of biallelic mutations in the ALDH3A2. The management of SLS largely remains symptomatic currently. However, several potential therapeutic options are being developed, keeping in view of the fundamental metabolic defects or correcting the genetic defect. This review aims to summarize the clinical, genetic and biochemical findings, pathogenetic mechanisms and the current therapeutic options, in SLS.

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“…We tried to understand why some patients show a milder phenotype, because this might contribute to a better understanding of the disease mechanisms underlying SLS. Enzyme activity measurements were not useful for this purpose because there is no clear correlation between residual enzyme activity and clinical phenotype . Because FALDH is a member of a large family of aldehyde dehydrogenases, most available enzyme assays are not 100% specific for FALDH activity.…”

Section: Discussionmentioning

confidence: 99%

Sjögren‐Larsson syndrome: The mild end of the phenotypic spectrum

et al. 2020

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Sjögren-Larsson syndrome (SLS) is a rare inborn error of lipid metabolism. The syndrome is caused by mutations in the ALDH3A2 gene, resulting in a deficiency of fatty aldehyde dehydrogenase. Most patients have a clearly recognizable severe phenotype, with congenital ichthyosis, intellectual disability, and spastic diplegia. In this study, we describe two patients with a remarkably mild phenotype. In both patients, males with actual ages of 45 and 61 years, the diagnosis was only established at an adult age. Their skin had been moderately affected from childhood onward, and both men remained ambulant with mild spasticity of their legs. Cognitive development, as reflected by school performance and professional career, had been unremarkable. Magnetic resonance spectroscopy of the first patient was lacking the characteristic lipid peak. We performed a literature search to identify additional SLS patients with a mild phenotype. We compared the clinical, radiologic, and molecular features of the mildly affected patients with the classical phenotype. We found 10 cases in the literature with a molecular proven diagnosis and a mild phenotype. Neither a genotype-phenotype correlation nor an alternative explanation for the

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Genotype and phenotype variability in Sjögren-Larsson syndrome

Cited by 25 publications

References 76 publications

Taraxacum officinale extract ameliorates dextran sodium sulphate‐induced colitis by regulating fatty acid degradation and microbial dysbiosis

Taraxacum officinale extract ameliorates dextran sodium sulphate‐induced colitis by regulating fatty acid degradation and microbial dysbiosis

<p>Sjogren-Larsson Syndrome: Mechanisms and Management</p>

Sjögren‐Larsson syndrome: The mild end of the phenotypic spectrum

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