Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus.
We have found mutations in the Menkes disease gene (MNK) which impair, but do not abolish, correct mRNA splicing in patients with less severe clinical phenotypes. In one family, four males aged 2-36 years with a distinctive Menkes variant have a mutation at the +3 position of a splice donor site near the 3' end of the Menkes coding sequence that is associated with exon skipping and a stable mutant transcript. In an unrelated 15-year-old male with typical occipital horn syndrome, a point mutation at the -2 exonic position of a splice donor site in the middle of the gene causes exon-skipping and activation of a cryptic splice acceptor site. In both mutations, maintenance of some normal splicing is demonstrable by RT-PCR, cDNA sequencing and ribonuclease protection.
Kaler
S G
SG
Section on Human Biochemical Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Gallo
L K
LK
Proud
V K
VK
Percy
A K
AK
Mark
Y
Y
Segal
N A
NA
Goldstein
D S
DS
Holmes
C S
CS
Gahl
W A
WA
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics*; D000293:Adolescent; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D002478:Cells, Cultured; D002570:Ceruloplasmin / Q000032:analysis; D003300:Copper / Q000097:blood; D000073840:Copper-Transporting ATPases; D004252:DNA Mutational Analysis; D004295:Dihydroxyphenylalanine / Q000097:blood / Q000134:cerebrospinal fluid; D004535:Ehlers-Danlos Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000145:classification / Q000235:genetics*; D005091:Exons; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008297:Male; D007706:Menkes Kinky Hair Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000097:blood / Q000134:cerebrospinal fluid; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009777:Occipital Bone / Q000002:abnormalities*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013728:Terminator Regions, Genetic
C486201:Atp7a protein, mouse; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D011993:Recombinant Fusion Proteins; D008734:Methoxyhydroxyphenylglycol; D004295:Dihydroxyphenylalanine; D003300:Copper; D002570:Ceruloplasmin; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases; C010117:3,4-dihydroxyphenylglycol