Novel ANKH amino terminus mutation (Pro5Ser) associated with early-onset calcium pyrophosphate disease with associated phosphaturia.
This report describes a 32-year-old woman presenting since childhood with progressive calcium pyrophosphate disease (CPPD), characterized by severe arthropathy and chondrocalcinosis involving multiple peripheral joints and intervertebral disks. Because ANKH mutations have been previously described in familial CPPD, the proband's DNA was assessed at this locus by direct sequencing of promoter and coding regions and revealed 3 sequence variants in ANKH. Sequences of exon 1 revealed a novel isolated nonsynonymous mutation (c.13 C>T), altering amino acid in codon 5 from proline to serine (CCG>TCG). Sequencing of parental DNA revealed an identical mutation in the proband's father but not the mother. Subsequent clinical evaluation demonstrated extensive chondrocalcinosis and degenerative arthropathy in the proband's father. In summary, we report a novel mutation, not previously described, in ANKH exon 1, wherein serine replaces proline, in a case of early-onset severe CPPD associated with metabolic abnormalities, with similar findings in the proband's father.
Mount Sinai School of Medicine, New York, NY, USA. BGruber.LIBJ@gmail.com
Barry L
BL
Gruber
Ana Rita
AR
Couto
Jácome Bruges
JB
Armas
Matthew A
MA
Brown
Kathleen
K
Finzel
Robert A
RA
Terkeltaub
D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D002131:Calcium Pyrophosphate / Q000652:urine; D002805:Chondrocalcinosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000652:urine; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006074:Gout Suppressants / Q000627:therapeutic use; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D007015:Hypophosphatemia, Familial / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D028061:Phosphate Transport Proteins / Q000235:genetics*; D011239:Prednisolone / Q000627:therapeutic use; D011859:Radiography
C498770:ANKH protein, human; D018501:Antirheumatic Agents; D005938:Glucocorticoids; D006074:Gout Suppressants; D028061:Phosphate Transport Proteins; D006886:Hydroxychloroquine; D011239:Prednisolone; D002131:Calcium Pyrophosphate