title: Clinical and genetic characteristics of mexican patients with juvenile presentation of niemann-pick type C disease.
abstract: Niemann-Pick type C disease (NPC) is a rare lysosomal disease with a protean presentation, ranging from a fatal neonatal course with visceromegaly to an adult presentation with only neurological or psychiatric symptomatology. In this report we describe the genetic and clinical characteristics of 3 Mexican patients from different families with juvenile presentation of NPC. Clinical examination, imaging of central nervous and gastrointestinal system, and EEG were performed. Genetic studies include sequencing and deletion/duplication analysis of NPC1 and NPC2 genes. All patients presented with cognitive impairment, ataxia, and supranuclear vertical gaze palsy; one case had gelastic cataplexy. Also they developed epilepsy and cortical atrophy and two patients had thinning of corpus callosum. The 3 patients were compound heterozygotes for NPC1 sequence variants, including 5 missense and 1 nonsense mutations: p.P1007A and p.F1087L in Case 1; p.Q921P and p.G992R in Case 2; and p.R348∗ and p.V1165M in case 3. Mexican patients with juvenile NPC presented with a variable clinical phenotype and compound heterozygosity. This suggests a relative high frequency of mutation carriers as it is reported for European population. Consequently, clinicians should consider NPC as a diagnosis possibility in any adolescent or young adult patient with juvenile dementia and/or ataxia, even in absence of gelastic cataplexy and supranuclear vertical gaze palsy.
authors.affiliation: Department of Medical Genetics, Centro Médico Nacional "20 de Noviembre", ISSSTE, San Lorenzo No. 502E, Colonia del Valle Sur, Del. Benito Juárez, 03100 México, DF, Mexico.
authors.forename: Raul E
authors.initials: RE
authors.lastname: Piña-Aguilar
authors.affiliation: Department of Medical Genetics, Centro Médico Nacional "20 de Noviembre", ISSSTE, San Lorenzo No. 502E, Colonia del Valle Sur, Del. Benito Juárez, 03100 México, DF, Mexico.
authors.forename: Aurea
authors.initials: A
authors.lastname: Vera-Loaiza
authors.affiliation: Department of Genetics-Research Unit, Instituto de Oftalmología "Conde de Valenciana", Chimalpopoca No. 14, Colonia Obrera, Del. Cuauhtémoc, 06800 México, DF, Mexico.
authors.forename: Oscar F
authors.initials: OF
authors.lastname: Chacón-Camacho
authors.affiliation: Department of Genetics-Research Unit, Instituto de Oftalmología "Conde de Valenciana", Chimalpopoca No. 14, Colonia Obrera, Del. Cuauhtémoc, 06800 México, DF, Mexico ; Department of Biochemistry, Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Ciudad Universitaria, Del. Coyoacán, 04510 México, DF, Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Zenteno
authors.affiliation: Department of Adult Neurology, Centro Médico Nacional "20 de Noviembre", ISSSTE, Félix Cuevas No. 540, Colonia del Valle Sur, Del. Benito Juárez, 03229 México, DF, Mexico.
authors.forename: Lilia
authors.initials: L
authors.lastname: Nuñez-Orozco
authors.affiliation: Department of Medical Genetics, Centro Médico Nacional "20 de Noviembre", ISSSTE, San Lorenzo No. 502E, Colonia del Valle Sur, Del. Benito Juárez, 03100 México, DF, Mexico.
authors.forename: Yuritzi
authors.initials: Y
authors.lastname: Santillán-Hernández