Molecular screening of Batten disease: identification of a missense mutation (E295K) in the CLN3 gene.
Batten disease, the juvenile form of neuronal ceroid lipofuscinosis, is a prevalent neuron degenerative disorder of childhood. A 1.02-kb genomic deletion in the Batten disease gene CLN3 has been determined to be a common mutation. We developed a PCR method to screen for this deletion and tested 43 Batten disease probands. We found 36% (31/86) of Batten disease chromosomes did not carry the 1.02-kb deletion. Of the three heterozygotes for the 1.02-kb deletion, a novel G-to-A missense mutation at nucleotide 1020 of the CLN3 cDNA sequence was found on two of the non-1.02-kb deletion chromosomes. The missense mutation resulted in a substitution of glutamic acid (E) by lysine (K) at position 295 (E295 K). The E295 K mutation causes a change in predicted local protein conformation. This glutamic acid is a highly conserved acidic amino acid, being present in human, mouse, dog and yeast, which suggests it may play an important role in the function of the Batten disease protein.
Zhong
N
N
Department of Human Genetics, New York State Institute for Basic Research, Staten Island 10314, USA. OMRDDZHONG@AOL.COM
Wisniewski
K E
KE
Kaczmarski
A L
AL
Ju
W
W
Xu
W M
WM
Xu
W W
WW
Mclendon
L
L
Liu
B
B
Kaczmarski
W
W
Sklower Brooks
S S
SS
Brown
W T
WT
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D004285:Dogs; D017353:Gene Deletion; D005820:Genetic Testing; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000235:genetics; D008562:Membrane Glycoproteins; D051379:Mice; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*
C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D011506:Proteins; D018698:Glutamic Acid; D008239:Lysine