Abstract：
Brachyolmia is a skeletal disorder with an autosomal mode of inheritance (both dominant and recessive) in which the patients have a short height, scoliosis and a reduced trunk size.
From the Muzaffargarh District in Pakistan, a consanguineous family with multiple Brachyolmia-affected subjects were enrolled in the present study. Basic epidemiological data and radiographs were collected for the subjects. Whole exome sequencing (WES) which was followed by Sanger sequencing was applied to report the geneticbasic of Brachyolmia.
The WES identified a missense mutation (c.1037 G > C, p. R346P) in exon 9 of the PAPSS2 gene that was confirmed by the Sanger sequencing in the enrolled subjects. The mutation followed a Mendalian pattern with an autosomal recessive inheritance mode. Multiple sequence alignment by Clustal Omega indicated that the PAPSS2 mutation-containing domain is highly conserved. The HEK293T whole-cell extract that was transfected with the Myc-tagged PCMV6-PAPSS2 of both the wild and mutant constructs were resolved by SDS-PAGE as well as by a Western blot, which confirmed that there are different PAPSS2 protein expression patterns when they were compared between the control and Brachyolmia patients. This difference between the normal and mutated protein was not evident when the three-dimensional computational structures were generated using homology modeling.
We report a missense mutation (c.1037 G > C, p. R346P) in the PAPSS2 gene that caused Brachyolmia in a consanguineous Pakistani family.
From the Muzaffargarh District in Pakistan, a consanguineous family with multiple Brachyolmia-affected subjects were enrolled in the present study. Basic epidemiological data and radiographs were collected for the subjects. Whole exome sequencing (WES) which was followed by Sanger sequencing was applied to report the geneticbasic of Brachyolmia.
The WES identified a missense mutation (c.1037 G > C, p. R346P) in exon 9 of the PAPSS2 gene that was confirmed by the Sanger sequencing in the enrolled subjects. The mutation followed a Mendalian pattern with an autosomal recessive inheritance mode. Multiple sequence alignment by Clustal Omega indicated that the PAPSS2 mutation-containing domain is highly conserved. The HEK293T whole-cell extract that was transfected with the Myc-tagged PCMV6-PAPSS2 of both the wild and mutant constructs were resolved by SDS-PAGE as well as by a Western blot, which confirmed that there are different PAPSS2 protein expression patterns when they were compared between the control and Brachyolmia patients. This difference between the normal and mutated protein was not evident when the three-dimensional computational structures were generated using homology modeling.
We report a missense mutation (c.1037 G > C, p. R346P) in the PAPSS2 gene that caused Brachyolmia in a consanguineous Pakistani family.
摘要：
Brachyolmia是一种具有常染色体遗传模式（显性和隐性）的骨骼疾病，其中患者身高较短，脊柱侧弯和躯干尺寸减小。
来自巴基斯坦的Muzaffargarh区，本研究纳入了一个近亲家庭,该家庭有多个受影响的Brachyolmia的受试者.收集受试者的基本流行病学数据和X射线照片。应用全外显子组测序（WES），然后进行Sanger测序，以报告Brachyolmia的遗传学基础。
WES鉴定出一个错义突变（c.1037G>C，p。R346P）在PAPSS2基因的外显子9中，通过Sanger测序在招募的受试者中得到证实。突变遵循常染色体隐性遗传模式的门达利模式。ClustalOmega的多重序列比对表明含PAPSS2突变的结构域是高度保守的。用野生型和突变体构建体的Myc标记的PCMV6-PAPSS2转染的HEK293T全细胞提取物通过SDS-PAGE以及通过蛋白质印迹进行解析。这证实了在对照组和Brachyolmia患者之间进行比较时，PAPSS2蛋白表达模式不同。当使用同源性建模产生三维计算结构时,正常蛋白和突变蛋白之间的这种差异并不明显。
我们报告了一个错义突变(c.1037G>C，p。R346P）在PAPSS2基因中引起近缘性巴基斯坦家庭中的Brachyolmia。
来自巴基斯坦的Muzaffargarh区，本研究纳入了一个近亲家庭,该家庭有多个受影响的Brachyolmia的受试者.收集受试者的基本流行病学数据和X射线照片。应用全外显子组测序（WES），然后进行Sanger测序，以报告Brachyolmia的遗传学基础。
WES鉴定出一个错义突变（c.1037G>C，p。R346P）在PAPSS2基因的外显子9中，通过Sanger测序在招募的受试者中得到证实。突变遵循常染色体隐性遗传模式的门达利模式。ClustalOmega的多重序列比对表明含PAPSS2突变的结构域是高度保守的。用野生型和突变体构建体的Myc标记的PCMV6-PAPSS2转染的HEK293T全细胞提取物通过SDS-PAGE以及通过蛋白质印迹进行解析。这证实了在对照组和Brachyolmia患者之间进行比较时，PAPSS2蛋白表达模式不同。当使用同源性建模产生三维计算结构时,正常蛋白和突变蛋白之间的这种差异并不明显。
我们报告了一个错义突变(c.1037G>C，p。R346P）在PAPSS2基因中引起近缘性巴基斯坦家庭中的Brachyolmia。
