Sensorineural hearing-loss in the Smith–Lemli-Opitz syndrome

Berardino, Federica Di; Alpini, D.; Ambrosetti, Umberto; Amadeo, Chiara; Cesarani, Antonio

doi:10.1016/j.pedex.2007.05.002

Cited by 7 publications

(6 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increasing evidences had suggested the importance of lipid/cholesterol-homeostasis in auditory function. Some genetic syndromes, such as Niemann-Pick type C and Smith-Lemli-Opitz, that affect cholesterol intracellular transport/synthesis display devastating neurological phenotypes including SNHL 46,47 . The epidemiology studies had suggested the potential association of hypercholesterolemia and SNHL.…”

Section: Discussionmentioning

confidence: 99%

Deletion of OSBPL2 in auditory cells increases cholesterol biosynthesis and drives reactive oxygen species production by inhibiting AMPK activity

et al. 2019

View full text Add to dashboard Cite

Oxysterol-binding protein like 2 ( OSBPL2 ) was identified as a novel causal gene for autosomal dominant nonsyndromic hearing loss. However, the pathogenesis of OSBPL2 deficits in ADNSHL was still unclear. The function of OSBPL2 as a lipid-sensing regulator in multiple cellular processes suggested that OSBPL2 might play an important role in the regulation of cholesterol-homeostasis, which was essential for inner ear. In this study the potential roles of OSBPL2 in cholesterol biosynthesis and ROS production were investigated in Osbpl2 -KO OC1 cells and osbpl2b -KO zebrafish. RNA-seq-based analysis suggested that OSBPL2 was implicated in cholesterol biosynthesis and AMPK signaling pathway. Furthermore, Osbpl2/osbpl2b -KO resulted in a reduction of AMPK activity and up-regulation of Srebp2/srebp2, Hmgcr/hmgcr and Hmgcs1/hmgcs1 , key genes in the sterol biosynthetic pathway and associated with AMPK signaling. In addition, OSBPL2 was also found to interact with ATIC, key activator of AMPK. The levels of total cholesterol and ROS in OC1 cells or zebrafish inner ear were both increased in Osbpl2/osbpl2b -KO mutants and the mitochondrial damage was detected in Osbpl2 -KO OC1 cells. This study uncovered the regulatory roles of OSBPL2 in cellular cholesterol biosynthesis and ROS production. These founds might contribute to the deep understanding of the pathogenesis of OSBPL2 mutation in ADNSHL.

show abstract

Section: Discussionmentioning

confidence: 99%

Deletion of OSBPL2 in auditory cells increases cholesterol biosynthesis and drives reactive oxygen species production by inhibiting AMPK activity

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Sterol disorders such as Smith-Lemli-Opitz syndrome [3] and Niemann-Pick Type C disease [4] display devastating central neurological phenotypes. These conditions also include sensorineural (peripheral) hearing loss as a part of the spectrum.…”

Section: Introductionmentioning

confidence: 99%

Hearing Loss and Hair Cell Death in Mice Given the Cholesterol-Chelating Agent Hydroxypropyl-β-Cyclodextrin

et al. 2012

View full text Add to dashboard Cite

Cyclodextrins are sugar compounds that are increasingly finding medicinal uses due to their ability to complex with hydrophobic molecules. One cyclodextrin in particular, 2-hydroxypropyl-β-cyclodextrin (HPβCD), is used as a carrier to solubilize lipophilic drugs and is itself being considered as a therapeutic agent for treatment of Niemann-Pick Type C disease, due to its ability to mobilize cholesterol. Results from toxicological studies suggest that HPβCD is generally safe, but a recent study has found that it causes hearing loss in cats. Whether the hearing loss occurred via death of cochlear hair cells, rendering it permanent, was unexplored. In the present study, we examined peripheral auditory function and cochlear histology in mice after subcutaneous injection of HPβCD to test for hearing loss and correlate any observed auditory deficits with histological findings. On average, auditory brainstem response thresholds were elevated at 4, 16, and 32 kHz in mice one week after treatment with 8,000 mg/kg. In severely affected mice all outer hair cells were missing in the basal half of the cochlea. In many cases, surviving hair cells in the cochlear apex exhibited abnormal punctate distribution of the motor protein prestin, suggesting long term changes to membrane composition and integrity. Mice given a lower dose of 4,000 mg/kg exhibited hearing loss only after repeated doses, but these threshold shifts were temporary. Therefore, cyclodextrin-induced hearing loss was complex, involving cell death and other more subtle influences on cochlear physiology.

show abstract

“…The association of hearing loss and lipid profile has also been studied by analysing genetic conditions with cholesterol homeostasis dysregulation. Conditions affecting cholesterol intracellular transport and synthesis like Smith-Lemli-Opitz syndrome and Niemann–Pick disease have been found to be associated with sensorineural hearing loss ( Berardino et al., 2007 , King et al., 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Does dyslipidemia worsen the hearing level in diabetics?

et al. 2017

View full text Add to dashboard Cite

ObjectiveTo identify the effect of dyslipidemia on auditory function detected by Pure Tone Audiometry. To check if dyslipidemia worsens the hearing level in diabetics.DesignThis was a comparative study where 120 subjects between the age group of 20 and 50 years underwent pure tone audiometry, lipid profile and blood sugars. Group 1 consisted of 30 subjects with type 2 diabetes and dyslipidemia; Group 2 had 30 subjects with isolated diabetes; Group 3 had 30 with isolated dyslipidemia and Group 4 included 30 normal subjects as control.ResultsSignificant hearing loss was seen only in the group with isolated diabetes (63%). The most common type of hearing loss was high frequency sensorineural hearing loss. When comparison was made between the combinations of different lipid profiles, no association was found to the level of hearing.ConclusionsDiabetics are more prone to high frequency hearing loss. Altered lipid profile has no role in causing hearing loss.

show abstract

Sensorineural hearing-loss in the Smith–Lemli-Opitz syndrome

Cited by 7 publications

References 23 publications

Deletion of OSBPL2 in auditory cells increases cholesterol biosynthesis and drives reactive oxygen species production by inhibiting AMPK activity

Deletion of OSBPL2 in auditory cells increases cholesterol biosynthesis and drives reactive oxygen species production by inhibiting AMPK activity

Hearing Loss and Hair Cell Death in Mice Given the Cholesterol-Chelating Agent Hydroxypropyl-β-Cyclodextrin

Does dyslipidemia worsen the hearing level in diabetics?

Contact Info

Product

Resources

About