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Background  Skeletal dysplasia is a heterogeneous group of disorders resulting from different genetic variants in humans. The current study was designed to identify the genetic causes of skeletal dysplasia and short stature in two consanguineous families from Pakistan, both comprised of multiple affected individuals. Patients in one family had proportionate short stature with reduced head circumference while affected individuals in the other family had disproportionate short stature.    Methods  Clinical data were obtained and radiological examinations of the index patients were completed. Whole genome sequencing for probands from both families were performed followed by Sanger sequencing to confirm segregation of identified variants in the respective families. In-silico pathogenicity score prediction for identified variant and amino acid conservation analysis was completed.    Results  Whole Genome Sequencing identified a known biallelic variant c.6176_6189delGTCAGCTGCCGAAG; p.(Gln2060ArgfsTer48) in  PCNT  gene and a novel biallelic variant c.174delC; p.(Asp60ThrfsTer7) in  RAB33B  gene respectively in affected members of the two families. Clinical imaging revealed platyspondyly and varus deformity in the legs of the affected members in the first family. Radiographs indicated severe platyspondyly, genu valgus deformity of legs and pectus carinatum for the patients in the second family.    Conclusion  In this study we report the phenotypes and genetic variants in two unrelated families with two distinct forms of skeletal dysplasia. This study strengthens the previous findings that patients harboring  PCNT  variants are phenotypically homogeneous and also extends the genotypic spectrum of  RAB33B  variants.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12891-021-04503-2.

RAB33B and PCNT variants in two Pakistani families with skeletal dysplasia and short stature