0026 Genetic Loci in Periodic Hypersomnia/Kleine-Levin Syndrome Type

Rp, Hillary; Ollila, H. M.; Faraco, Juliette; Lin, Liu; Dauvilliers, Yves; Han, Fang; Huang, Hsuan-Rong; Arnulf, Isabelle; Mignot, Emmanuel

doi:10.1093/sleepj/zsx050.025

Cited by 3 publications

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“…KLS is also reported to be associated with HLA‐DQB1*02 (Dauvilliers et al, ), but this association was difficult to replicate (Arnulf et al, ; Lavault et al, ; Nguyen et al, ). A recent genome‐wide association study found a variant in TRANK1 associated with KLS (Hillary et al, ). So far no mutation is identified in KLS and comprehensive genetic analysis of affected individuals is lacking (Raizen & Wu, ).…”

Section: Introductionmentioning

confidence: 99%

Kleine‐Levin syndrome is associated with LMOD3 variants

Shareef

Basit

et al. 2018

Journal of Sleep Research

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Kleine-Levin syndrome (KLS) is a rare periodic hypersomnia with associated behavioural abnormalities but with often favourable prognosis. There is excess risk of KLS in first-degree relatives, suggesting a strong genetic contribution. So far, no mutation is identified in KLS and comprehensive genetic analysis of affected individuals is lacking. Here we performed whole genome single-nucleotide polymorphism (SNP) genotyping and exome sequencing in a large family with seven affected members. The identified gene with a mutation was resequenced in 38 sporadic KLS patients and the expression of the gene product was mapped in the mouse brain. Linkage analysis mapped the disease locus to chromosome 3 and exome analysis identified a heterozygous missense variant in LMOD3 (p.E142D) in the linkage interval. The variant was found to segregate in all affected and one presumably unaffected member of the family. Resequencing LMOD3 in 38 other KLS patients and their families revealed three other low frequency or rare missense variants in seven cases that were inherited with incomplete penetrance. LMOD3 is expressed in the brain and colocalized with major structures involved in the regulation of vigilance states. LMOD proteins are structural proteins and seem to be developmentally regulated. Our findings suggest that KLS might be a structural/neurodevelopmental brain disease.

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Section: Introductionmentioning

confidence: 99%

Kleine‐Levin syndrome is associated with LMOD3 variants

Shareef

Basit

et al. 2018

Journal of Sleep Research

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Different circadian rest–active rhythms in Kleine-Levin syndrome: a prospective and case–control study

Lin

Chin

Huang

et al. 2021

Sleep

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Study objectives Kleine-Levin-syndrome (KLS) is a rare recurrent hypersomnia. Our study aimed at monitoring the movements of patients with KLS using actigraphy and evaluating their circadian rhythm. Methods Twenty young patients with KLS and 14 age-matched controls were recruited. Each individual wore an actigraphy for more than 6 months to monitor at least two attacks. Controls kept wearing the device for at least 7 days. The activity counts were averaged in hourly basis and the day-to-night amplitude was quantified by the differences of the averaged activity counts during daytime and nighttime. The hourly activities of different days were aligned and averaged to construct the circadian profile. Parametric and nonparametric estimation of circadian rhythm was calculated. We applied detrended fluctuation analysis to evaluate the temporal correlations beneath the activity fluctuations at multiple time scales. Results Circadian rhythm in asymptomatic period showed no significant difference compared to the controls. During hypersomnia attack, the amplitude of the circadian rest-active rhythms drastically decreased and decreased inter-daily stability (IS) was found, as well as significant decreased M10 and short-time fractal correlation (α1). Drastically decreased mean and standard deviation of activity were noted, compared to the pre-attack phase and recovery phase.α1 and M10 increased during the late attack phase, and overcompensated IS was noted in the recovery phase. Conclusions This study confirmed that circadian rest-active rhythms was affected when KLS hypersomnia attack. Several parameters including M10, IS and α1 may be physiological markers of KLS, which can help to predict the end of hypersomnia episodes.

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Breathing abnormalities during sleep in Kleine–Levin Syndrome

Gadoth

2018

Current Opinion in Pulmonary Medicine

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0026 Genetic Loci in Periodic Hypersomnia/Kleine-Levin Syndrome Type

Cited by 3 publications

References 0 publications

Kleine‐Levin syndrome is associated with LMOD3 variants

Kleine‐Levin syndrome is associated with LMOD3 variants

Different circadian rest–active rhythms in Kleine-Levin syndrome: a prospective and case–control study

Breathing abnormalities during sleep in Kleine–Levin Syndrome

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