Smith-Lemli-Opitz syndrome: clinical and biochemical findings in Brazilian patients

Scalco, Fernanda B.; Otto, Paulo Alberto; Brunetti, Iguatemy Lourenço; Cruzes, Vania M.; Moretti-Ferreira, Danilo

doi:10.1590/s1415-47572006000300003

Cited by 3 publications

(1 citation statement)

References 47 publications

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“…Most of the increases in the 75 µM AY9944 treated fish were in the brain and lower jaw regions as seen from the lateral orientation, with increases seen from the dorsal viewpoint in the olfactory bulb, optic tectum, and hindbrain, seen from both orientations. It is not surprising to see changes in ganglioside GM1 concentrations in the lower jaw of the zebrafish as facial developmental abnormalities are common in SLOS; in particular, micrognathia (small lower jaw) has been observed in more than 2/3rds of SLOS patients, indicating that this structure is particularly susceptible to loss of DHCR7 activity (Scalco et al 2006 ). In the 75 µM trazodone treated fish we observed increased staining in the olfactory bulb and hindbrain, and also in the eye, which could be related to the trazodone-induced retinal area defect (Fig.…”

Section: Resultsmentioning

confidence: 99%

Visualisation of cholesterol and ganglioside GM1 in zebrafish models of Niemann–Pick type C disease and Smith–Lemli–Opitz syndrome using light sheet microscopy

Cook

Bladen

Smith

et al. 2020

Histochem Cell Biol

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Lysosomal storage diseases are the most common cause of neurodegeneration in children. They are characterised at the cellular level by the accumulation of storage material within lysosomes. There are very limited therapeutic options, and the search for novel therapies has been hampered as few good small animal models are available. Here, we describe the use of light sheet microscopy to assess lipid storage in drug and morpholino induced zebrafish models of two diseases of cholesterol homeostasis with lysosomal dysfunction: First, Niemann–Pick type C disease (NPC), caused by mutations in the lysosomal transmembrane protein NPC1, characterised by intralysosomal accumulation of cholesterol and several other lipids. Second, Smith–Lemli–Opitz syndrome (SLOS), caused by mutations in 7-dehydrocholesterol reductase, which catalyses the last step of cholesterol biosynthesis and is characterised by intralysosomal accumulation of dietary cholesterol. This is the first description of a zebrafish SLOS model. We find that zebrafish accurately model lysosomal storage and disease-specific phenotypes in both diseases. Increased cholesterol and ganglioside GM1 were observed in sections taken from NPC model fish, and decreased cholesterol in SLOS model fish, but these are of limited value as resolution is poor, and accurate anatomical comparisons difficult. Using light sheet microscopy, we were able to observe lipid changes in much greater detail and identified an unexpected accumulation of ganglioside GM1 in SLOS model fish. Our data demonstrate, for the first time in zebrafish, the immense potential that light sheet microscopy has in aiding the resolution of studies involving lysosomal and lipid disorders.

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Section: Resultsmentioning

confidence: 99%