Novel carbohydrate sulfotransferase 3 mutation causing spondyloepiphyseal dysplasia with congenital joint dislocations in a Chinese family

Yan, Wenjin; Dai, Jin; Shi, Dongquan; Xu, X J; Chen, Dongyang; Xu, Zhihong; Song, Kai; Yao, Yao; Teng, Huajian; Jiang, Qing

doi:10.21037/aoj.2017.01.02

Cited by 3 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, hip dislocation has been associated with several genetic disorders, such as Schwartz-Jampel syndrome, spondyloepiphyseal dysplasia with congenital joint dislocations, or progressive pseudorheumatoid dysplasia, reinforcing the suspected role of genetics. [34][35][36] Genetic testing may provide an effective method for the early diagnosis of DDH, and to avoid population stratification in case-control studies, patients and healthy controls must be properly matched. 37,38 In the present study, UQCC1 TXNDC8 TXNDC8 TUBE1 TTC39C TTC39C TSPAN18 TSPAN18 TSPAN13 TSPAN13 TSPAN11 TRPM3 TRPM3 TRAPPC11 TP53INP1 TP53INP1 TOP2B TOP2B TNFRSF10B TNFRSF10B TMPRSS12 TMPRSS12 TMEM254-AS1 TMEM254-AS1 TLL1 TLL1 TLE3 TLE3 TKT TICRR TICRR TGFBR3 TGFBR3 TEX10 TENM3 TENM3 TCOF1 TCOF1 TBXAS1 TBXAS1 TBX1 TBX1 TBC1D32 TBC1D32 TBC1D1 TBC1D1 TARS TARS TAF8 TAF8 TAAR6 The protein-protein interaction (PPI) analysis conducted by using GeNets for DDH-associated genes.…”

Section: Discussionmentioning

confidence: 99%

“…The wide range of variation in incidence rates has been attributed to the differences in diagnostic methods and the timing of evaluation. Moreover, hip dislocation has been associated with several genetic disorders, such as Schwartz‐Jampel syndrome, spondyloepiphyseal dysplasia with congenital joint dislocations, or progressive pseudorheumatoid dysplasia, reinforcing the suspected role of genetics . Genetic testing may provide an effective method for the early diagnosis of DDH, and to avoid population stratification in case‐control studies, patients and healthy controls must be properly matched .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A genome‐wide association study identifies new genes associated with developmental dysplasia of the hip

Yan

Zheng²,

Tang

et al. 2019

Clinical Genetics

Self Cite

View full text Add to dashboard Cite

Developmental dysplasia of the hip (DDH) is one of the most common congenital malformations and covers a spectrum of hip disorders from mild dysplasia to irreducible dislocation. The pathological mechanisms of DDH are poorly understood, which hampers the development of diagnostic tools and treatments. To gain insight into its disease mechanism, we explored the potential biological processes that underlie DDH by integrating pathway analysis tools and performing a genome-wide association study (GWAS). A total of 406 DDH-associated genes (P < 0.001) were identified by our GWAS using a Chinese Han cohort consisting of 386 DDH cases and 500 healthy controls (Set A). We verified the significant loci (P < 10 −5 ) in another Chinese Han cohort consisting of 574 DDH patients and 569 healthy controls (Set B). An intronic Single Nucleotide Polymorphism (SNP) (rs61930502) showed significant association in Set A and Set B (P = 2.65 × 10 −7 and 2.0 × 10 −4 , respectively). The minor allele, rs61930502-A, which tended to prevent DDH showed a dominant effect. Heat shock 70 kDa protein 8 (HSPA8) showed the most direct interactions with other proteins which were coded by DDH-associated genes in the protein-protein interaction analysis. Interestingly, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested a relation between DDH and the genes involved in type II diabetes mellitus pathway (P = 0.0067). Our genetic and protein interaction evidence could open avenues for future studies of DDH. K E Y W O R D Sdevelopmental dysplasia of the hip, genome-wide association study, heat shock 70 kDa protein 8, rs61930502, type II diabetes mellitus pathway Wenjin Yan, Zheng Hao, and Shuyan Tang are contributed equally to this work.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A genome‐wide association study identifies new genes associated with developmental dysplasia of the hip

Yan

Zheng²,

Tang

et al. 2019

Clinical Genetics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cardiac valvular insufficiencies in the form of mitral regurge and tricuspid regurge were found in Patients 5, 6, and 8. Valvular dysplasia was previously reported in patients with CHST3 mutations (Hall, 1997; Rajab et al, 2004; Tuysuz et al, 2009; Unger et al, 2010; Yan et al, 2017). However, in our study, a severe cardiac disease was noted in Patient 6 who died at the age of 4 years due to severe pulmonary hypertension and heart failure.…”

Section: Discussionmentioning

confidence: 80%

CHST3‐related skeletal dysplasia in 14 patients: Identification of 8 novel variants and further expansion of the phenotypic spectrum

Otaify

Elhossini

Abdel‐Ghafar

et al. 2023

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Biallelic variants in CHST3 gene result in congenital dislocation of large joints, club feet, short stature, rhizomelia, kypho-scoliosis, platyspondyly, epiphyseal dysplasia, flared metaphysis, in addition to minor cardiac lesions and hearing loss. Herein, we describe 14 new patients from 11 unrelated Egyptian families with CHST3-related skeletal dysplasia. All patients had spondyloepiphyseal changes that were progressive with age in addition to bifid distal ends of humeri which can be considered a diagnostic key in patients with CHST3 variants. They also shared peculiar facies with broad forehead, broad nasal tip, long philtrum and short neck. Rare unusual associated findings included microdontia, teeth spacing, delayed eruption, prominent angulation of the lumbar-sacral junction and atrial septal defect. Mutational analysis revealed 10 different homozygous CHST3 (NM_004273.5) variants including 7 missense, two frameshift and one nonsense variant. Of them, the c.384_391dup (p.Pro131Argfs*88) was recurrent in two families. Eight of these variants were not described before. Our study presents the largest series of patients with CHST3-related skeletal dysplasia from the same ethnic group. Furthermore, it reinforces that lethal cardiac involvement is a critical clinical finding of the disorder. Therefore, we believe that our study expands the phenotypic and mutational spectrum, and also highlights the importance of performing echocardiography in patients harboring CHST3 variants.

show abstract

“…This report provides further evidence for the cardiac involvement in this condition. First reported by Kozlowski et al (1974), cardiac defects including hypertrophy of both atria and ventricle, thickening of mitral valve leaflet, aortic regurgitation, and stenosis were noted in several reports (Hall, 1997;Otaify et al, 2023;Rajab et al, 2004;Srivastava et al, 2017;Tuysuz et al, 2009;Unger et al, 2010;Yan et al, 2017). It appears that mitral, tricuspid, and aortic valves are commonly affected in that order with thickened leaflets, stenosis, and insufficiency.…”

Section: Discussionmentioning

confidence: 98%

Indian patients with CHST3‐related chondrodysplasia with congenital joint dislocations

Singh,

Jacob,

Patil

et al. 2023

American J of Med Genetics Pt A

View full text Add to dashboard Cite

CHST3‐related chondrodysplasia with congenital joint dislocations (CDCJD, #MIM 143095), is a rare genetic skeletal disorder caused by biallelic loss of function variants in CHST3. CHST3 is critical for the sulfation of chondroitin sulfate. This study delineates the clinical presentation of nine individuals featuring the key symptoms of CDCJD; congenital joint (knee and elbow) dislocations, short trunk short stature progressive vertebral anomalies, and metacarpal shortening. Additional manifestations include irregular distal femoral epiphysis, supernumerary carpal ossification centers, bifid humerus, club foot, and cardiac abnormalities. Sanger sequencing was carried out to investigate molecular etiology in eight patients and exome sequencing in one. Genetic testing revealed five homozygous variants in CHST3 (four were novel and one was previously reported). All these variants are located on sulfotransferase domain of CHST3 protein and were classified as pathogenic/ likely pathogenic. We thus report on nine individuals with CHST3‐related chondrodysplasia with congenital joint dislocations from India and suggest monitoring the health of cardiac valves in this condition.

show abstract

Novel carbohydrate sulfotransferase 3 mutation causing spondyloepiphyseal dysplasia with congenital joint dislocations in a Chinese family

Cited by 3 publications

References 0 publications

A genome‐wide association study identifies new genes associated with developmental dysplasia of the hip

A genome‐wide association study identifies new genes associated with developmental dysplasia of the hip

CHST3‐related skeletal dysplasia in 14 patients: Identification of 8 novel variants and further expansion of the phenotypic spectrum

Indian patients with CHST3‐related chondrodysplasia with congenital joint dislocations

Contact Info

Product

Resources

About