Abstract：
Dysferlinopathies are autosomal recessive muscular dystrophies resulting from defects in DYSF (MIM: 603009), which is located on chromosome 2p13 and encodes the dysferlin protein.
We performed exome sequencing and subsequent trio-based analysis in a family with dysferlinopathy.
We report a young patient presenting with hyperCKemia and mild muscle weakness of the lower limbs. Exome sequencing of the proband revealed a homozygous frameshift mutation, NM_001130987.2:c.1471dupA(p.M491Nfs*15), in DYSF. The father was heterozygous for the mutation and the mother did not carry the mutation, as determined by genetic analyses, exome sequencing of parental samples, and a trio-based analysis. Further analysis revealed that the DYSF gene was not deleted; instead, the entire chromosome 2 of the proband was inherited from the father. Thus, the child had paternal uniparental isodisomy for chromosome 2 (uniparental disomy [UPD]2 pat).
We report the first case of dysferlinopathy caused by paternal isodisomy for chromosome 2. Furthermore, our findings highlight the importance of exome sequencing of the proband and parents and trio analyses in clinical settings, particularly when Mendelian inheritance cannot be confirmed, to identify the presence of UPD and to rule out large pathogenic deletions.
We performed exome sequencing and subsequent trio-based analysis in a family with dysferlinopathy.
We report a young patient presenting with hyperCKemia and mild muscle weakness of the lower limbs. Exome sequencing of the proband revealed a homozygous frameshift mutation, NM_001130987.2:c.1471dupA(p.M491Nfs*15), in DYSF. The father was heterozygous for the mutation and the mother did not carry the mutation, as determined by genetic analyses, exome sequencing of parental samples, and a trio-based analysis. Further analysis revealed that the DYSF gene was not deleted; instead, the entire chromosome 2 of the proband was inherited from the father. Thus, the child had paternal uniparental isodisomy for chromosome 2 (uniparental disomy [UPD]2 pat).
We report the first case of dysferlinopathy caused by paternal isodisomy for chromosome 2. Furthermore, our findings highlight the importance of exome sequencing of the proband and parents and trio analyses in clinical settings, particularly when Mendelian inheritance cannot be confirmed, to identify the presence of UPD and to rule out large pathogenic deletions.
摘要：
背景：Dysferlinopathies是由DYSF缺陷引起的常染色体隐性遗传性肌营养不良（MIM：603009），它位于染色体2p13上，编码dysferlin蛋白。
方法：我们在一个患有异常铁蛋白病的家庭中进行了外显子组测序和随后的基于三重奏的分析。
结果：我们报告了一名年轻患者，表现为高CK血症和下肢轻度肌无力。先证者的外显子组测序显示纯合移码突变，NM_001130987.2：c.1471dupA（p。M491Nfs*15),在DYSF。父亲是突变的杂合子，母亲没有携带突变，根据基因分析，亲本样本的外显子组测序，和基于三重奏的分析。进一步的分析表明，DYSF基因没有被删除；相反，先证者的整个2号染色体是从父亲那里继承的。因此，该孩子有2号染色体的父系单亲同体（单亲同体[UPD]2pat）。
结论：我们报告了首例由2号染色体父系等异体性引起的异常酶病。此外，我们的研究结果强调了先证者和父母的外显子组测序和三重奏分析在临床环境中的重要性，特别是当孟德尔遗传无法确认时，以确定UPD的存在并排除大的致病性缺失。
方法：我们在一个患有异常铁蛋白病的家庭中进行了外显子组测序和随后的基于三重奏的分析。
结果：我们报告了一名年轻患者，表现为高CK血症和下肢轻度肌无力。
结论：我们报告了首例由2号染色体父系等异体性引起的异常酶病。
