Abstract：
OBJECTIVE: Genetic disorders involved in skeleton system arise due to the disturbance in skeletal development, growth and homeostasis. Filamin B is an actin binding protein which is large dimeric protein which cross link actin cytoskeleton filaments into dynamic structure. A single nucleotide changes in the FLNB gene causes spondylocarpotarsal synostosis syndrome, a rare bone disorder due to which the fusion of carpels and tarsals synostosis occurred along with fused vertebrae. In the current study we investigated a family residing in north-western areas of Pakistan.
METHODS: The whole exome sequencing of proband was performed followed by Sanger sequencing of all family members of the subject to validate the variant segregation within the family. Bioinformatics tools were utilized to assess the pathogenicity of the variant.
RESULTS: Whole Exome Sequencing revealed a novel variant (NM_001457: c.209C>T and p.Pro70Leu) in the FLNB gene which was homozygous missense mutation in the FLNB gene. The variant was further validated and visualized by Sanger sequencing and protein structure studies respectively as mentioned before.
CONCLUSIONS: The findings have highlighted the importance of the molecular diagnosis in SCT (spondylocarpotarsal synostosis syndrome) for genetic risk counselling in consanguineous families.
METHODS: The whole exome sequencing of proband was performed followed by Sanger sequencing of all family members of the subject to validate the variant segregation within the family. Bioinformatics tools were utilized to assess the pathogenicity of the variant.
RESULTS: Whole Exome Sequencing revealed a novel variant (NM_001457: c.209C>T and p.Pro70Leu) in the FLNB gene which was homozygous missense mutation in the FLNB gene. The variant was further validated and visualized by Sanger sequencing and protein structure studies respectively as mentioned before.
CONCLUSIONS: The findings have highlighted the importance of the molecular diagnosis in SCT (spondylocarpotarsal synostosis syndrome) for genetic risk counselling in consanguineous families.
摘要：
目的：涉及骨骼系统的遗传疾病是由于骨骼发育障碍而引起的，生长和体内平衡。FilaminB是一种肌动蛋白结合蛋白，是一种大型二聚体蛋白，将肌动蛋白细胞骨架丝交联成动态结构。FLNB基因的单核苷酸变化导致脊骨滑膜综合征，一种罕见的骨骼疾病，因此与融合的椎骨一起发生心皮和tarsals融合。在当前的研究中，我们调查了居住在巴基斯坦西北部地区的一个家庭。
方法：先证者的全外显子组测序，然后对受试者的所有家族成员进行Sanger测序，以验证家族内的变异分离。生物信息学工具用于评估变体的致病性。
结果:全外显子组测序揭示了FLNB基因中的新变体(NM_001457:c.209C>T和p.Pro70Leu),其在FLNB基因中是纯合错义突变。如前所述,分别通过Sanger测序和蛋白质结构研究进一步验证和可视化变体。
结论：研究结果强调了分子诊断在SCT（脊骨关节滑脱综合征）中对近亲家庭遗传风险咨询的重要性。
方法：先证者的全外显子组测序，然后对受试者的所有家族成员进行Sanger测序，以验证家族内的变异分离。生物信息学工具用于评估变体的致病性。
结果:全外显子组测序揭示了FLNB基因中的新变体(NM_001457:c.209C>T和p.Pro70Leu),其在FLNB基因中是纯合错义突变。如前所述,分别通过Sanger测序和蛋白质结构研究进一步验证和可视化变体。
结论：研究结果强调了分子诊断在SCT（脊骨关节滑脱综合征）中对近亲家庭遗传风险咨询的重要性。
