RAB33B and PCNT variants in two Pakistani families with skeletal dysplasia and short stature.
MOPDII
Pakistan
Short stature
Skeletal dysplasia
Smith-McCort dysplasia
Whole genome sequencing
Journal
BMC musculoskeletal disorders
ISSN: 1471-2474
Titre abrégé: BMC Musculoskelet Disord
Pays: England
ID NLM: 100968565
Informations de publication
Date de publication:
20 Jul 2021
20 Jul 2021
Historique:
received:
18
02
2021
accepted:
01
07
2021
entrez:
21
7
2021
pubmed:
22
7
2021
medline:
23
7
2021
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 34284742
doi: 10.1186/s12891-021-04503-2
pii: 10.1186/s12891-021-04503-2
pmc: PMC8293541
doi:
Substances chimiques
RAB33B protein, human
EC 3.6.1.-
rab GTP-Binding Proteins
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
630Informations de copyright
© 2021. The Author(s).
Références
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