Published in:
Open Access
01-12-2022 | Scoliosis | Research
Biallelic variants in CHST3 cause Spondyloepiphyseal dysplasia with joint dislocations in three Pakistani kindreds
Authors:
Mehran Kausar, Noor Ul Ain, Farzana Hayat, Hunain Fatima, Saad Azim, Hazrat Ullah, Murva Mushtaq, Sumbal Khalid, Shahid Hussain, Sadaf Naz, Jamal Janjua, Saad Bin Amjad, Ruqia Mehmood Baig, Outi Makitie, Raheel Qamar, Shiro Ikegawa, Nishimura Gen, Chiea Chuen Khor, Jia Nee Foo, Saima Siddiqi
Published in:
BMC Musculoskeletal Disorders
|
Issue 1/2022
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Abstract
Background
Skeletal dysplasia is a heterogeneous group of disorders. Spondyloepiphyseal dysplasias comprise one subgroup. Deficiency of carbohydrate sulfotransferase 3 has been reported in a small number of patients with recessively inherited spondyloepiphyseal dysplasia with joint dislocation, short stature and scoliosis. We report here molecular and clinical findings of affected individuals in three consanguineous Pakistani families. Affected individuals in all three families had a uniform phenotype including severe short stature, multiple dislocated joints, progressive scoliosis and facial dysmorphism.
Methods
Clinical evaluation was done for three unrelated families. Radiological survey of bones was completed for patients from two of the families. Whole exome sequencing index patients from each family was performed followed by Sanger sequencing for validation of segregation of identified variants in respective families. In-silico analysis for determining pathogenicity of identified variants and conservation was done.
Results
Whole-exome sequencing revealed biallelic variants c.590 T > C;p.(Leu197Pro), c.603C > A;p.(Tyr201Ter) and c.661C > T;p.(Arg221Cys) in CHST3 (NM_004273.5) in the three families with eight, five and two affected individuals, respectively. Contrary to previous reports, affected individuals in none of the families exhibited a hearing loss.
Conclusion
We describe genotypic and phenotypic findings of three unrelated families with spondyloepiphyseal dysplasia. Our study confirms phenotypic variability and adds to the genotypic spectrum of spondyloepiphyseal dysplasia.