PDF(Pubmed)
Abstract：
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: 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: 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.
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.
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: 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.
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.
摘要：
背景：骨骼发育不良是一组异质性疾病。脊椎骨phy发育不良包括一个亚组。据报道，少数隐性遗传性脊柱骨phy发育不良伴关节脱位的患者存在碳水化合物磺基转移酶3缺乏，身材矮小和脊柱侧弯。我们在此报告三个近亲巴基斯坦家庭中受影响个体的分子和临床发现。所有三个家庭的受影响个体均具有统一的表型，包括严重的身材矮小，多个关节脱臼,进行性脊柱侧弯和面部畸形。
方法：对三个无关家庭进行临床评估。对来自两个家庭的患者完成了骨骼的放射学调查。对来自每个家族的患者进行全外显子组测序索引,随后进行Sanger测序,以验证在各自家族中鉴定的变体的分离。进行用于确定鉴定的变体和保守性的致病性的计算机内分析。
结果：全外显子组测序显示双等位基因变异c.590T>C;p.（Leu197Pro），c.603C>A；p.（Tyr201Ter）和c.661C>T；p。（Arg221Cys）在CHST3（NM_004273.5）中的三个家族中有八个，五个和两个受影响的人，分别。与以前的报告相反，没有一个家庭的受影响个人表现出听力损失。
结论：我们描述了三个不相关的脊柱骨骨发育不良家庭的基因型和表型发现。我们的研究证实了表型变异性，并增加了脊柱骨发育不良的基因型谱。
方法：对三个无关家庭进行临床评估。对来自两个家庭的患者完成了骨骼的放射学调查。对来自每个家族的患者进行全外显子组测序索引,随后进行Sanger测序,以验证在各自家族中鉴定的变体的分离。进行用于确定鉴定的变体和保守性的致病性的计算机内分析。
结果：全外显子组测序显示双等位基因变异c.590T>C;p.（Leu197Pro），c.603C>A；p.（Tyr201Ter）和c.661C>T；p。（Arg221Cys）在CHST3（NM_004273.5）中的三个家族中有八个，五个和两个受影响的人，分别。与以前的报告相反，没有一个家庭的受影响个人表现出听力损失。
结论：我们描述了三个不相关的脊柱骨骨发育不良家庭的基因型和表型发现。我们的研究证实了表型变异性，并增加了脊柱骨发育不良的基因型谱。
