TY - JOUR
T1 - Indian patients with CHST3-related chondrodysplasia with congenital joint dislocations
AU - Singh, Swati
AU - Jacob, Prince
AU - Patil, Siddaramappa J.
AU - Muranjan, Mamta
AU - Shah, Hitesh
AU - Girisha, Katta M.
AU - Bhavani, Gandham Sri Lakshmi
N1 - Publisher Copyright:
© 2023 Wiley Periodicals LLC.
PY - 2023/10/24
Y1 - 2023/10/24
N2 - CHST3-related chondrodysplasia with congenital joint dislocations (CDCJD, #MIM 143095), is a rare genetic skeletal disorder caused by biallelic loss of function variants in CHST3. CHST3 is critical for the sulfation of chondroitin sulfate. This study delineates the clinical presentation of nine individuals featuring the key symptoms of CDCJD; congenital joint (knee and elbow) dislocations, short trunk short stature progressive vertebral anomalies, and metacarpal shortening. Additional manifestations include irregular distal femoral epiphysis, supernumerary carpal ossification centers, bifid humerus, club foot, and cardiac abnormalities. Sanger sequencing was carried out to investigate molecular etiology in eight patients and exome sequencing in one. Genetic testing revealed five homozygous variants in CHST3 (four were novel and one was previously reported). All these variants are located on sulfotransferase domain of CHST3 protein and were classified as pathogenic/ likely pathogenic. We thus report on nine individuals with CHST3-related chondrodysplasia with congenital joint dislocations from India and suggest monitoring the health of cardiac valves in this condition.
AB - CHST3-related chondrodysplasia with congenital joint dislocations (CDCJD, #MIM 143095), is a rare genetic skeletal disorder caused by biallelic loss of function variants in CHST3. CHST3 is critical for the sulfation of chondroitin sulfate. This study delineates the clinical presentation of nine individuals featuring the key symptoms of CDCJD; congenital joint (knee and elbow) dislocations, short trunk short stature progressive vertebral anomalies, and metacarpal shortening. Additional manifestations include irregular distal femoral epiphysis, supernumerary carpal ossification centers, bifid humerus, club foot, and cardiac abnormalities. Sanger sequencing was carried out to investigate molecular etiology in eight patients and exome sequencing in one. Genetic testing revealed five homozygous variants in CHST3 (four were novel and one was previously reported). All these variants are located on sulfotransferase domain of CHST3 protein and were classified as pathogenic/ likely pathogenic. We thus report on nine individuals with CHST3-related chondrodysplasia with congenital joint dislocations from India and suggest monitoring the health of cardiac valves in this condition.
KW - CHST3
KW - chondrodysplasia with congenital joint dislocations
KW - congenital joint dislocations
KW - short stature
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UR - https://www.mendeley.com/catalogue/51a249dd-45f6-3039-bc8f-e0cd6307762b/
U2 - 10.1002/ajmg.a.63422
DO - 10.1002/ajmg.a.63422
M3 - Article
C2 - 37876363
AN - SCOPUS:85174630850
SN - 1552-4825
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
ER -