PURPOSE: Niemann-Pick disease type C (NP-C) is an autosomal recessive lipid storage disease manifested by an impairment in cellular cholesterol homeostasis. The clinical phenotype of NP-C is extremely variable, ranging from an acute neonatal form to an adult late-onset presentation. To facilitate phenotype-genotype studies, we have analyzed multiple Israeli NP-C families. METHODS: The severity of the disease was assessed by the age at onset, hepatic involvement, neurological deterioration, and cholesterol esterification studies. Screening of the entire NPC1 coding sequence allowed for molecular characterization and identification of disease causing mutations. RESULTS: A total of nine NP-C index cases with mainly neurovisceral involvement were characterized. We demonstrated a possible link between the severity of the clinical phenotype and the cholesterol esterification levels in fibroblast cultures following 24 hours of in vitro cholesterol loading. In addition, we identified eight novel mutations in the NPC1 gene. CONCLUSIONS: Our results further support the clinical and allelic heterogeneity of NP-C and point to possible association between the clinical and the biochemical phenotype in distinct affected Israeli families.
PURPOSE: Niemann-Pick disease type C (NP-C) is an autosomal recessive lipid storage disease manifested by an impairment in cellular cholesterol homeostasis. The clinical phenotype of NP-C is extremely variable, ranging from an acute neonatal form to an adult late-onset presentation. To facilitate phenotype-genotype studies, we have analyzed multiple Israeli NP-C families. METHODS: The severity of the disease was assessed by the age at onset, hepatic involvement, neurological deterioration, and cholesterol esterification studies. Screening of the entire NPC1 coding sequence allowed for molecular characterization and identification of disease causing mutations. RESULTS: A total of nine NP-C index cases with mainly neurovisceral involvement were characterized. We demonstrated a possible link between the severity of the clinical phenotype and the cholesterol esterification levels in fibroblast cultures following 24 hours of in vitro cholesterol loading. In addition, we identified eight novel mutations in the NPC1 gene. CONCLUSIONS: Our results further support the clinical and allelic heterogeneity of NP-C and point to possible association between the clinical and the biochemical phenotype in distinct affected Israeli families.
Authors: Charles H Vite; Jessica H Bagel; Gary P Swain; Maria Prociuk; Tracey U Sikora; Veronika M Stein; Patricia O'Donnell; Therese Ruane; Sarah Ward; Alexandra Crooks; Su Li; Elizabeth Mauldin; Susan Stellar; Marc De Meulder; Mark L Kao; Daniel S Ory; Cristin Davidson; Marie T Vanier; Steven U Walkley Journal: Sci Transl Med Date: 2015-02-25 Impact factor: 17.956
Authors: William S Garver; David Jelinek; F John Meaney; James Flynn; Kathleen M Pettit; Glen Shepherd; Randall A Heidenreich; Cate M Walsh Vockley; Graciela Castro; Gordon A Francis Journal: J Lipid Res Date: 2009-09-09 Impact factor: 5.922
Authors: Blair R Roszell; Jian-Qin Tao; Kevin J Yu; Ling Gao; Shaohui Huang; Yue Ning; Sheldon I Feinstein; Charles H Vite; Sandra R Bates Journal: PLoS One Date: 2013-07-02 Impact factor: 3.240