COMP and Col9A3 mutations and their relationship to the pseudoachondroplasia phenotype.
While pseudoachondroplasia (PSACH) is almost exclusively caused by cartilage oligomeric matrix protein (COMP) mutations, many patients identified with the PSACH phenotype do not have this mutation, suggesting gene and locus heterogeneity. In order to further characterize this entity, we studied 32 clinically and radiographically diagnosed PSACH patients, among 19 families. COMP and collagen (Col) IX (A1, A2 and A3) mutations, were determined. Patients who tested negative for pathological gene mutations but who were identified with the PSACH phenotype, were included. The phenotypes were characterized according to height deviation (cm) from normal, lower extremity mechanical axis deviation (MAD), cervical and thoracolumbar spine involvement, pelvic index, as well as hip, knee, ankle and hand involvement. We report an 81% mutation detection rate for PSACH, of which COMP+Col9A3 mutations were more prevalent (61%) than COMP mutations alone (30%). Of our PSACH patients, 19% tested negative for both COMP and Col9A3 mutations, and they presented with the greatest mean height deviations, but the least mean MADs. While all the PSACH mutations consistently produced the severe phenotype, the V426A mutation in Col9A3 produced the most severe. Mother-daughter and father-son phenotypic similarities were noted in the COMP+Col9A3 families. Col9A3 and gender play confounding roles in the phenotypic severity of PSACH. The presence of the PSACH phenotype in patients who tested negative for known mutations further confirms the genetic heterogeneity of this condition.
College of Health Science, Korea University, Seoul, Republic of Korea.
Woon-Won
WW
Jung
Gracia Cielo
GC
Balce
Jae-Woo
JW
Cho
Sung-Chul
SC
Jung
Suk-Joo
SJ
Hong
Hae-Ryong
HR
Song
D000130:Achondroplasia / Q000000981:diagnostic imaging / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D001827:Body Height / Q000235:genetics; D064236:Cartilage Oligomeric Matrix Protein; D002648:Child; D002675:Child, Preschool; D024081:Collagen Type IX / Q000235:genetics* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007723:Korea; D008297:Male; D064235:Matrilin Proteins; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011859:Radiography
C120768:COL9A3 protein, human; D064236:Cartilage Oligomeric Matrix Protein; D024081:Collagen Type IX; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human