Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis.
Familial tumoral calcinosis (FTC; OMIM 211900) is a severe autosomal recessive metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Using linkage analysis, we mapped the gene underlying FTC to 2q24-q31. This region includes the gene GALNT3, which encodes a glycosyltransferase responsible for initiating mucin-type O-glycosylation. Sequence analysis of GALNT3 identified biallelic deleterious mutations in all individuals with FTC, suggesting that defective post-translational modification underlies the disease.
Topaz
Orit
O
Department of Dermatology, Rambam Medical Center, Haifa, Israel.
Shurman
Daniel L
DL
Bergman
Reuven
R
Indelman
Margarita
M
Ratajczak
Paulina
P
Mizrachi
Mordechai
M
Khamaysi
Ziad
Z
Behar
Doron
D
Petronius
Dan
D
Friedman
Vered
V
Zelikovic
Israel
I
Raimer
Sharon
S
Metzker
Arieh
A
Richard
Gabriele
G
Sprecher
Eli
E
D001483:Base Sequence; D002114:Calcinosis / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D004247:DNA / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005808:Genes, Recessive; D006031:Glycosylation; D006801:Humans; D008297:Male; D009077:Mucins / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D011499:Protein Processing, Post-Translational; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D004247:DNA; D009077:Mucins; D017350:N-Acetylgalactosaminyltransferases; D009363:Neoplasm Proteins; D000097763:Polypeptide N-acetylgalactosaminyltransferase