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

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Ain , N U , Fatima , Z , Naz , S & Mäkitie , O 2021 , ' RAB33B and PCNT variants in two Pakistani families with skeletal dysplasia and short stature ' , BMC Musculoskeletal Disorders , vol. 22 , no. 1 , 630 . https://doi.org/10.1186/s12891-021-04503-2

Title: RAB33B and PCNT variants in two Pakistani families with skeletal dysplasia and short stature
Author: Ain, Noor ul; Fatima, Zunaira; Naz, Sadaf; Mäkitie, Outi
Contributor organization: HUS Children and Adolescents
Lastentautien yksikkö
Children's Hospital
Date: 2021-07-20
Language: eng
Number of pages: 6
Belongs to series: BMC Musculoskeletal Disorders
ISSN: 1471-2474
DOI: https://doi.org/10.1186/s12891-021-04503-2
URI: http://hdl.handle.net/10138/334234
Abstract: 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.
Subject: Skeletal dysplasia
Short stature
Whole genome sequencing
Smith-McCort dysplasia
3126 Surgery, anesthesiology, intensive care, radiology
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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