Medical Genetics Lab of Dr. Zeinali, Kawsar Human Genetics Research Center, Tehran, Iran.
Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Arch Iran Med. 2021 Dec 1;24(12):887-896. doi: 10.34172/aim.2021.133.
Hemophilia A (HA) is an X-linked recessive bleeding disorder with a high rate of genetic heterogeneity. The present study was conducted on a large cohort of Iranian HA patients and data obtained from databases.
A total of 622 Iranian HA patients from 329 unrelated families who had been referred to a medical genetics laboratory in Tehran from 2005 to 2019, were enrolled in this retrospective, observational study. Genetic screening of pathogenic variants of the gene was performed using inverse shifting PCR, direct sequencing, and multiplex ligation-dependent amplification (MLPA). Point mutation frequencies in different exons were analyzed for our samples as well as 6031 HA patients whose data were recorded in a database.
A total of 144 different pathogenic or likely pathogenic variants including 29 novel variants were identified. A strategy to decrease costs of genetic testing of HA was suggested based on this finding.
This study provides comprehensive information on pathogenic/likely pathogenic variants in Iranian HA patients which improves the spectrum of causative mutations and can be helpful to clinicians and medical geneticists in counseling and molecular diagnosis of HA.
血友病 A（HA）是一种 X 连锁隐性遗传性出血性疾病，具有较高的遗传异质性。本研究对来自伊朗的大量 HA 患者进行了研究，并从数据库中获得了数据。
本回顾性观察性研究共纳入了 329 个无关家庭的 622 名来自德黑兰医学遗传学实验室的伊朗 HA 患者。使用反转移位 PCR、直接测序和多重连接依赖性扩增（MLPA）对基因的致病性变异进行了基因筛查。分析了我们样本以及数据库中记录的 6031 名 HA 患者不同外显子中的点突变频率。
共鉴定出 144 种不同的致病性或可能致病性变异，包括 29 种新变异。基于这一发现，提出了一种降低 HA 基因检测成本的策略。
本研究提供了伊朗 HA 患者致病性/可能致病性变异的全面信息，提高了致病突变的谱，有助于临床医生和医学遗传学家对 HA 的咨询和分子诊断。
