title: Compound heterozygous genotype is associated with protracted juvenile neuronal ceroid lipofuscinosis.
abstract: We present a clinicopathological study and the first molecular genetic analysis of a family with 2 siblings affected by a rare, protracted form of juvenile neuronal ceroid lipofuscinosis (JNCL). Molecular genetic studies showed that both siblings, in addition to being heterozygous for the 1.02-kb CLN3 deletion, a common mutation in JNCL, also had a G-to-A missense mutation at nucleotide 1,020 of the CLN3 cDNA sequence on the non-1.02-kb deletion chromosomes. This point mutation resulted in a substitution of glutamic acid by lysine at position 295 of the CLN3 protein. Thus, a single point mutation at residue 295 of the CLN3 protein in protracted JNCL may underlie the phenotype in this form, which differs from that in classic JNCL.
authors.affiliation: Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Wisniewski
authors.forename: N
authors.initials: N
authors.lastname: Zhong
authors.forename: W
authors.initials: W
authors.lastname: Kaczmarski
authors.forename: A
authors.initials: A
authors.lastname: Kaczmarski
authors.forename: E
authors.initials: E
authors.lastname: Kida
authors.forename: W T
authors.initials: WT
authors.lastname: Brown
authors.forename: K O
authors.initials: KO
authors.lastname: Schwarz
authors.forename: A M
authors.initials: AM
authors.lastname: Lazzarini
authors.forename: A J
authors.initials: AJ
authors.lastname: Rubin
authors.forename: E S
authors.initials: ES
authors.lastname: Stenroos
authors.forename: W G
authors.initials: WG
authors.lastname: Johnson
authors.forename: T M
authors.initials: TM
authors.lastname: Wisniewski
mesh_terms: D000328:Adult; D004569:Electroencephalography; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D008967:Molecular Biology; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree; D012867:Skin / Q000473:pathology