PDF(Pubmed)
Abstract：
Cystic fibrosis (CF) is an autosomal recessive disease caused by the inheritance of two mutant cystic fibrosis transmembrane conductance regulator (CFTR) alleles, one from each parent. Autosomal recessive disorders are rarely associated with germline mutations or mosaicism. Here, we propose a case of paternal germline mutation causing CF. The subject also had an identifiable maternal mutant allele. We identified the compound heterozygous variants in the proband through Sanger sequencing, and in silico studies predicted functional effects on the protein. Also, short tandem repeat markers revealed the de novo nature of the mutation. The maternal mutation in the CFTR gene was c.1000C > T. The de novo mutation was c.178G > A, p.Glu60Lys. This mutation is located in the lasso motif of the CFTR protein and, according to in silico structural analysis, disrupts the interaction of the lasso motif and R-domain, thus influencing protein function. This first reported case of de novo mutation in Asia has notable implications for molecular diagnostics, genetic counseling, and understanding the genetic etiology of recessive disorders in the Iranian population.
Identifying the first de novo mutation in the cystic fibrosis transmembrane conductance regulator protein in Iran: a case report with insights from microsatellite markersA child can develop Cystic Fibrosis (CF) if both parents pass on mutated genes. In some rare cases, new genetic mutations occur spontaneously, causing CF. This report discusses a unique case where a child has one gene with a spontaneous mutation and inherits another gene mutation from the mother. We used a method called Sanger sequencing to find the two different gene changes in the affected person. We also used computer analysis to predict how these changes might affect the protein responsible for this genetic disease. To confirm that the child\'s new change is not inherited, we used a type of genetic marker called microsatellite markers. The mutation inherited from the mother and the new spontaneous mutation resulted in a unique change in the responsible protein. This mutation is located in a specific part of the protein called the lasso motif. Our computer simulations show that this mutation disrupts the interaction between the lasso motif and another part of the protein called the R-domain, which ultimately affects the protein\'s function. This case is significant because it is the first reported instance of a de novo mutation causing CF in Asia. It has important implications for genetic testing, counseling, and understanding how recessive genetic disorders like CF occur within the Iranian population.
Identifying the first de novo mutation in the cystic fibrosis transmembrane conductance regulator protein in Iran: a case report with insights from microsatellite markersA child can develop Cystic Fibrosis (CF) if both parents pass on mutated genes. In some rare cases, new genetic mutations occur spontaneously, causing CF. This report discusses a unique case where a child has one gene with a spontaneous mutation and inherits another gene mutation from the mother. We used a method called Sanger sequencing to find the two different gene changes in the affected person. We also used computer analysis to predict how these changes might affect the protein responsible for this genetic disease. To confirm that the child\'s new change is not inherited, we used a type of genetic marker called microsatellite markers. The mutation inherited from the mother and the new spontaneous mutation resulted in a unique change in the responsible protein. This mutation is located in a specific part of the protein called the lasso motif. Our computer simulations show that this mutation disrupts the interaction between the lasso motif and another part of the protein called the R-domain, which ultimately affects the protein\'s function. This case is significant because it is the first reported instance of a de novo mutation causing CF in Asia. It has important implications for genetic testing, counseling, and understanding how recessive genetic disorders like CF occur within the Iranian population.
摘要：
囊性纤维化（CF）是由两个突变型囊性纤维化跨膜传导调节因子（CFTR）等位基因遗传引起的常染色体隐性遗传疾病，每个父母一个。常染色体隐性遗传疾病很少与种系突变或镶嵌性相关。这里,我们提出一例父系种系突变引起CF的病例。受试者还具有可鉴定的母体突变等位基因。我们通过Sanger测序鉴定了先证者中的复合杂合变体，并且在计算机研究中预测了对蛋白质的功能影响。此外，短串联重复标记揭示了突变的从头性质。CFTR基因的母体突变为c.1000C>T。从头突变为c.178G>A，p.Glu60Lys.此突变位于CFTR蛋白的套索基序中，根据硅结构分析，破坏套索基序和R域的相互作用，从而影响蛋白质的功能。这一亚洲首例报道的从头突变对分子诊断具有显著意义。遗传咨询,了解伊朗人群隐性疾病的遗传病因。
确定伊朗囊性纤维化跨膜传导调节蛋白中的第一个从头突变：从微卫星标记获得见解的病例报告如果父母双方都传递突变基因，儿童可以发展囊性纤维化（CF）。在一些罕见的情况下，新的基因突变自发发生，导致CF。本报告讨论了一个独特的案例，其中一个孩子有一个自发突变的基因，并从母亲那里继承了另一个基因突变。我们使用了一种称为Sanger测序的方法来发现受影响人的两种不同的基因变化。我们还使用计算机分析来预测这些变化如何影响导致这种遗传性疾病的蛋白质。要确认子项的新更改未被继承，我们使用了一种叫做微卫星标记的遗传标记。从母亲遗传的突变和新的自发突变导致负责蛋白质的独特变化。这种突变位于称为套索基序的蛋白质的特定部分。我们的计算机模拟表明，这种突变破坏了套索基序与蛋白质的另一部分R结构域之间的相互作用，最终影响蛋白质的功能。这种情况是重要的,因为它是在亚洲首次报道的引起CF的从头突变的实例。它对基因检测有重要意义，咨询,并了解伊朗人口中CF等隐性遗传疾病是如何发生的。
确定伊朗囊性纤维化跨膜传导调节蛋白中的第一个从头突变：从微卫星标记获得见解的病例报告如果父母双方都传递突变基因，儿童可以发展囊性纤维化（CF）。在一些罕见的情况下，新的基因突变自发发生，导致CF。本报告讨论了一个独特的案例，其中一个孩子有一个自发突变的基因，并从母亲那里继承了另一个基因突变。我们使用了一种称为Sanger测序的方法来发现受影响人的两种不同的基因变化。我们还使用计算机分析来预测这些变化如何影响导致这种遗传性疾病的蛋白质。要确认子项的新更改未被继承，我们使用了一种叫做微卫星标记的遗传标记。从母亲遗传的突变和新的自发突变导致负责蛋白质的独特变化。这种突变位于称为套索基序的蛋白质的特定部分。我们的计算机模拟表明，这种突变破坏了套索基序与蛋白质的另一部分R结构域之间的相互作用，最终影响蛋白质的功能。这种情况是重要的,因为它是在亚洲首次报道的引起CF的从头突变的实例。它对基因检测有重要意义，咨询,并了解伊朗人口中CF等隐性遗传疾病是如何发生的。
