Srour Myriam, Putorti Maria Lisa, Schwartzentruber Jeremy, Bolduc Véronique, Shevell Michael Israel, Poulin Chantal, O'ferrall Erin, Buhas Daniela, Majewski Jacek, Brais Bernard
Laboratory of Neurogenetics of Motion, Montreal Neurological Institute, McGill University, Montréal, Canada; Division of Pediatric Neurology, Montreal Children's Hospital-McGill University Health Center, Montréal, Canada.
Muscle Nerve. 2014 Nov;50(5):775-9. doi: 10.1002/mus.24224. Epub 2014 Sep 16.
We have identified a large consanguineous Lebanese family with 5 individuals with severe childhood-onset recessive sensory loss associated with deafness and variable optic atrophy.
Autozygosity mapping was performed in all affected individuals, followed by whole-exome sequencing (WES) in 2 individuals.
WES identified a homozygous missense mutation (c.916G>A, p.G306R) in the cerebral riboflavin transporter SLC52A2, recently shown to cause Brown-Vialetto-Van-Laere syndrome (BVVLS), which is considered primarily a motor neuronopathy. Our patients have a phenotype distinct from BVVLS, characterized by severe progressive sensory loss mainly affecting vibration and proprioception that evolves to include sensorineural hearing loss in childhood, variable degrees of optic atrophy, and marked upper extremity weakness and atrophy. Treatment of 3 patients with 400 mg/day riboflavin over 3 months produced definite clinical improvement.
Mutations in SLC52A2 result in a recognizable phenotype distinct from BVVLS. Early recognition of this disorder is critical, given its potential treatability.
我们鉴定出一个黎巴嫩近亲大家族，其中有5名个体患有严重的儿童期起病的隐性感觉丧失，并伴有耳聋和不同程度的视神经萎缩。
对所有患病个体进行纯合性定位分析，随后对2名个体进行全外显子组测序（WES）。
WES在脑核黄素转运体SLC52A2中鉴定出一个纯合错义突变（c.916G>A，p.G306R），最近研究表明该突变会导致Brown-Vialetto-Van-Laere综合征（BVVLS），该病主要被认为是一种运动神经元病。我们的患者具有与BVVLS不同的表型，其特征为严重的进行性感觉丧失，主要影响振动觉和本体感觉，在儿童期发展为包括感音神经性听力丧失、不同程度的视神经萎缩，以及明显的上肢无力和萎缩。3名患者接受每日400毫克核黄素治疗3个月后临床症状有明确改善。
SLC52A2突变导致一种与BVVLS不同的可识别表型。鉴于其潜在的可治疗性，早期识别这种疾病至关重要。
