Compound heterozygous genotype is associated with protracted juvenile neuronal ceroid lipofuscinosis.
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.
Wisniewski
K E
KE
Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA.
Zhong
N
N
Kaczmarski
W
W
Kaczmarski
A
A
Kida
E
E
Brown
W T
WT
Schwarz
K O
KO
Lazzarini
A M
AM
Rubin
A J
AJ
Stenroos
E S
ES
Johnson
W G
WG
Wisniewski
T M
TM
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