Biallelic variants in CHST3 cause Spondyloepiphyseal dysplasia with joint dislocations in three Pakistani kindreds.
CHST3
Chondroitin
Pakistan
Short stature
Spondyloepiphyseal dysplasia
Journal
BMC musculoskeletal disorders
ISSN: 1471-2474
Titre abrégé: BMC Musculoskelet Disord
Pays: England
ID NLM: 100968565
Informations de publication
Date de publication:
30 Aug 2022
30 Aug 2022
Historique:
received:
04
03
2022
accepted:
29
07
2022
entrez:
30
8
2022
pubmed:
31
8
2022
medline:
2
9
2022
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 36042462
doi: 10.1186/s12891-022-05719-6
pii: 10.1186/s12891-022-05719-6
pmc: PMC9426025
doi:
Substances chimiques
Sulfotransferases
EC 2.8.2.-
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
818Informations de copyright
© 2022. The Author(s).
Références
Nature. 2012 Nov 1;491(7422):56-65
pubmed: 23128226
Am J Med Genet A. 2004 May 1;126A(4):413-9
pubmed: 15098240
Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10155-60
pubmed: 15215498
Am J Med Genet A. 2019 Dec;179(12):2393-2419
pubmed: 31633310
Am J Med Genet A. 2010 Oct;152A(10):2543-9
pubmed: 20830804
Clin Genet. 2016 Jul;90(1):90-5
pubmed: 26572954
Nucleic Acids Res. 2012 Jul;40(Web Server issue):W452-7
pubmed: 22689647
FEBS Lett. 1998 Dec 18;441(2):235-41
pubmed: 9883891
Nat Methods. 2010 Apr;7(4):248-9
pubmed: 20354512
Am J Hum Genet. 2008 Jun;82(6):1368-74
pubmed: 18513679
J Biol Chem. 2002 Jan 11;277(2):1443-50
pubmed: 11696535
Clin Genet. 2009 Apr;75(4):375-83
pubmed: 19320654