PDF(Pubmed)
Abstract：
BACKGROUND: Alström syndrome (AS) represents an exceptionally rare genetic disorder characterized by a constellation of features including cardiomyopathy, progressive hearing and vision impairment, as well as obesity. This study seeks to elucidate the genetic underpinnings of this syndrome within the Saudi Arabian population.
METHODS: Employing an extended family cohort, we conducted an exhaustive molecular genetic assessment to delineate the presence of Alström syndrome. Additionally, we conducted an extensive review of existing literature from Saudi population to contextualize our findings within the broader understanding of the disorder in our country.
RESULTS: Within our studied extended family, we identified two individuals harboring the homozygous pathogenic mutation (c.2729C>G) in the ALMS1 gene [NM_015120.4:c.2729C>G (p.Ser910*)]. Notably, carrier status was observed in the parents, whereas some siblings exhibited typical alleles while others were carriers of the mutation. Intriguingly, a review of the literature unveiled six distinct reports documenting a total of 20 Alström syndrome patients within the Saudi Arabian population, each presenting with distinct novel mutations.
CONCLUSIONS: In cases featuring cardiomyopathy, obesity, and progressive hearing and vision loss, Alström syndrome merits inclusion within the differential diagnosis. To confirm the diagnosis, molecular genetic assessment of the ALMS1 gene is imperative, offering definitive clarity amidst the complex clinical presentation. This investigation reinforces the importance of genetic scrutiny for precise diagnosis and highlights the unique genetic landscape of Alström syndrome within the Saudi Arabian population.
METHODS: Employing an extended family cohort, we conducted an exhaustive molecular genetic assessment to delineate the presence of Alström syndrome. Additionally, we conducted an extensive review of existing literature from Saudi population to contextualize our findings within the broader understanding of the disorder in our country.
RESULTS: Within our studied extended family, we identified two individuals harboring the homozygous pathogenic mutation (c.2729C>G) in the ALMS1 gene [NM_015120.4:c.2729C>G (p.Ser910*)]. Notably, carrier status was observed in the parents, whereas some siblings exhibited typical alleles while others were carriers of the mutation. Intriguingly, a review of the literature unveiled six distinct reports documenting a total of 20 Alström syndrome patients within the Saudi Arabian population, each presenting with distinct novel mutations.
CONCLUSIONS: In cases featuring cardiomyopathy, obesity, and progressive hearing and vision loss, Alström syndrome merits inclusion within the differential diagnosis. To confirm the diagnosis, molecular genetic assessment of the ALMS1 gene is imperative, offering definitive clarity amidst the complex clinical presentation. This investigation reinforces the importance of genetic scrutiny for precise diagnosis and highlights the unique genetic landscape of Alström syndrome within the Saudi Arabian population.
摘要：
背景：Alström综合征（AS）是一种非常罕见的遗传性疾病，其特征包括心肌病，进行性听力和视力障碍，以及肥胖。这项研究旨在阐明沙特阿拉伯人群中该综合征的遗传基础。
方法：采用大家庭队列，我们进行了详尽的分子遗传学评估,以确定Alström综合征的存在.此外,我们对沙特人口的现有文献进行了广泛的回顾,以便在对我国疾病的更广泛理解中对我们的发现进行背景分析.
结果：在我们研究的大家庭中，我们确定了两个在ALMS1基因中具有纯合致病突变（c.2729C>G）的个体[NM_015120.4：c.2729C>G（p。Ser910*)].值得注意的是,在父母中观察到携带者状态，而一些兄弟姐妹表现出典型的等位基因，而另一些则是突变的携带者。有趣的是，对文献的回顾公布了六份不同的报告，记录了沙特阿拉伯人口中总共20名Alström综合征患者，每个都有不同的新突变。
结论：在以心肌病为特征的病例中，肥胖，进行性听力和视力丧失，Alström综合征值得纳入鉴别诊断。为了确认诊断，ALMS1基因的分子遗传学评估势在必行，在复杂的临床表现中提供明确的清晰度。这项调查加强了遗传审查对精确诊断的重要性，并突出了沙特阿拉伯人口中Alström综合征的独特遗传景观。
方法：采用大家庭队列，我们进行了详尽的分子遗传学评估,以确定Alström综合征的存在.此外,我们对沙特人口的现有文献进行了广泛的回顾,以便在对我国疾病的更广泛理解中对我们的发现进行背景分析.
结果：在我们研究的大家庭中，我们确定了两个在ALMS1基因中具有纯合致病突变（c.2729C>G）的个体[NM_015120.4：c.2729C>G（p。Ser910*)].值得注意的是,在父母中观察到携带者状态，而一些兄弟姐妹表现出典型的等位基因，而另一些则是突变的携带者。有趣的是，对文献的回顾公布了六份不同的报告，记录了沙特阿拉伯人口中总共20名Alström综合征患者，每个都有不同的新突变。
结论：在以心肌病为特征的病例中，肥胖，进行性听力和视力丧失，Alström综合征值得纳入鉴别诊断。为了确认诊断，ALMS1基因的分子遗传学评估势在必行，在复杂的临床表现中提供明确的清晰度。这项调查加强了遗传审查对精确诊断的重要性，并突出了沙特阿拉伯人口中Alström综合征的独特遗传景观。
