OBJECTIVE: To define the clinical and laboratory findings in a novel autosomal recessive white matter disorder called hypomyelination and congenital cataract, recently found to be caused by a deficiency of a membrane protein, hyccin, encoded by the DRCTNNB1A gene located on chromosome 7p21.3-p15.3. METHODS: We performed neurological examination, neurophysiological, neuroimaging, and neuropathological studies on sural nerve biopsy in 10 hypomyelination and congenital cataract patients from 5 unrelated families. RESULTS: The clinical picture was characterized by bilateral congenital cataract, developmental delay, and slowly progressive neurological impairment with spasticity, cerebellar ataxia, and mild-to-moderate mental retardation. Neurophysiological studies showed a slightly to markedly slowed motor nerve conduction velocity in 9 of 10 patients, and multimodal evoked potentials indicated increased central conduction times. Neuroimaging studies demonstrated a diffuse supratentorial hypomyelination, with in some patients, additional areas of more prominent signal change in the frontal region. Sural nerve biopsy showed a slight-to-severe reduction in myelinated fiber density, with several axons surrounded by a thin myelin sheath or devoid of myelin. INTERPRETATION: Hypomyelination and congenital cataract is a novel autosomal recessive white matter disorder characterized by the unique association of congenital cataract and hypomyelination of the central and peripheral nervous system.
OBJECTIVE: To define the clinical and laboratory findings in a novel autosomal recessive white matter disorder called hypomyelination and congenital cataract, recently found to be caused by a deficiency of a membrane protein, hyccin, encoded by the DRCTNNB1A gene located on chromosome 7p21.3-p15.3. METHODS: We performed neurological examination, neurophysiological, neuroimaging, and neuropathological studies on sural nerve biopsy in 10 hypomyelination and congenital cataract patients from 5 unrelated families. RESULTS: The clinical picture was characterized by bilateral congenital cataract, developmental delay, and slowly progressive neurological impairment with spasticity, cerebellar ataxia, and mild-to-moderate mental retardation. Neurophysiological studies showed a slightly to markedly slowed motor nerve conduction velocity in 9 of 10 patients, and multimodal evoked potentials indicated increased central conduction times. Neuroimaging studies demonstrated a diffuse supratentorial hypomyelination, with in some patients, additional areas of more prominent signal change in the frontal region. Sural nerve biopsy showed a slight-to-severe reduction in myelinated fiber density, with several axons surrounded by a thin myelin sheath or devoid of myelin. INTERPRETATION: Hypomyelination and congenital cataract is a novel autosomal recessive white matter disorder characterized by the unique association of congenital cataract and hypomyelination of the central and peripheral nervous system.
Authors: Marjan E Steenweg; Adeline Vanderver; Susan Blaser; Alberto Bizzi; Tom J de Koning; Grazia M S Mancini; Wessel N van Wieringen; Frederik Barkhof; Nicole I Wolf; Marjo S van der Knaap Journal: Brain Date: 2010-10 Impact factor: 13.501
Authors: Elisabetta Gazzerro; Simona Baldassari; Caterina Giacomini; Veronica Musante; Floriana Fruscione; Veronica La Padula; Roberta Biancheri; Sonia Scarfì; Valeria Prada; Federica Sotgia; Ian D Duncan; Federico Zara; Hauke B Werner; Michael P Lisanti; Lucilla Nobbio; Anna Corradi; Carlo Minetti Journal: PLoS One Date: 2012-03-26 Impact factor: 3.240
Authors: Jeremy M Baskin; Xudong Wu; Romain Christiano; Michael S Oh; Curtis M Schauder; Elisabetta Gazzerro; Mirko Messa; Simona Baldassari; Stefania Assereto; Roberta Biancheri; Federico Zara; Carlo Minetti; Andrea Raimondi; Mikael Simons; Tobias C Walther; Karin M Reinisch; Pietro De Camilli Journal: Nat Cell Biol Date: 2015-11-16 Impact factor: 28.824