INTRODUCTION: 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. METHODS: Autozygosity mapping was performed in all affected individuals, followed by whole-exome sequencing (WES) in 2 individuals. RESULTS: 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. CONCLUSIONS: Mutations in SLC52A2 result in a recognizable phenotype distinct from BVVLS. Early recognition of this disorder is critical, given its potential treatability.
INTRODUCTION: 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. METHODS: Autozygosity mapping was performed in all affected individuals, followed by whole-exome sequencing (WES) in 2 individuals. RESULTS: 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. CONCLUSIONS: Mutations in SLC52A2 result in a recognizable phenotype distinct from BVVLS. Early recognition of this disorder is critical, given its potential treatability.
Authors: Yanwei Xi; Christina Honeywell; Dapeng Zhang; Jeremy Schwartzentruber; Chandree L Beaulieu; Martine Tetreault; Taila Hartley; Jennifer Marton; Silvia M Vidal; Jacek Majewski; L Aravind; Michael Gollob; Kym M Boycott; Robert M Gow Journal: Int J Cardiol Date: 2015-03-11 Impact factor: 4.164
Authors: Kimberly A Aldinger; Stephen J Mosca; Martine Tétreault; Jennifer C Dempsey; Gisele E Ishak; Taila Hartley; Ian G Phelps; Ryan E Lamont; Diana R O'Day; Donald Basel; Karen W Gripp; Laura Baker; Mark J Stephan; Francois P Bernier; Kym M Boycott; Jacek Majewski; Jillian S Parboosingh; A Micheil Innes; Dan Doherty Journal: Am J Hum Genet Date: 2014-08-07 Impact factor: 11.025