Almohammadi Abdullah T, Radhwi Osman, AlAhwal Hatem, Barefah Ahmed, Bahashwan Salem, Ashankyty Ibraheem M, Almashjari Majed, Ayaz Rawan, Al-Marzouki Adel, Zaher Galila F, Hussain Hend, Samman Abeer A, Zakariyah Abeer
Hematology, King Abdulaziz University, Faculty of Medicine, Jeddah, SAU.
Hematology Research Unit, King Fahd Medical Research Center, Jeddah, SAU.
Cureus. 2023 Jul 17;15(7):e42038. doi: 10.7759/cureus.42038. eCollection 2023 Jul.
Hemophilia A (HA) is an X-linked recessive disorder that results from mutations in the factor VIII gene (FVIII). Most affected patients are males due to the inheritance of mutations in the FVIII gene from their mothers. Females are mostly found to be carriers unless they inherited the mutation from both parents. Obligate carriers of HA are mothers whose sons are affected with HA, or daughters who inherit the mutation from their affected fathers. A possible carrier of HA could be any female who has one or more affected relatives with HA in her family. Hemophilia A carriers (HACs) could present with similar symptoms to affected patients, including low factor VIII level, and risk of bleeding especially after surgical procedures or postpartum hemorrhage.
Assessing the phenotype of possible HAC and its association with genetic variants in the FVIII gene for better screening methods for HAC.
From the period between 25 June and 25 October 2021, the study was conducted at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. We recruited seven mothers whose sons were affected with HA, and 18 possible HAC who are relatives to sever affected patients with HA. All 25 candidates were assessed for the FVIII level, activated partial thromboplastin time (APTT), and bleeding risk and sequenced a part of Exon14 in their FVIII gene.
Twenty-five percent of the participants show a low level of FVIII, however, none of them have prolonged bleeding nor suffer from bleeding tendency. We also identified two missense variants in six of the candidates, but the clinical significance of these variants has not been determined previously.
This pilot study is the first to explore the phenotype of several HAC in Saudi Arabia. A larger scale study with more HA patients and their female relatives is needed to understand the correlation between phenotype and genotype for better screening for HAC.
甲型血友病（HA）是一种X连锁隐性疾病，由凝血因子VIII基因（FVIII）突变引起。由于男性从母亲那里遗传了FVIII基因突变，所以大多数受影响的患者为男性。女性大多为携带者，除非她们从父母双方都遗传了该突变。HA的必然携带者是儿子患HA的母亲，或者从患病父亲那里遗传了突变的女儿。HA的可能携带者可能是家族中有一个或多个患HA亲属的任何女性。甲型血友病携带者（HACs）可能出现与受影响患者相似的症状，包括FVIII水平低，尤其是在外科手术或产后出血后有出血风险。
评估可能的HAC的表型及其与FVIII基因遗传变异的关联，以获得更好的HAC筛查方法。
2021年6月25日至10月25日期间，在沙特阿拉伯吉达的阿卜杜勒阿齐兹国王大学医院进行了这项研究。我们招募了7名儿子患HA的母亲，以及18名与严重HA患者有亲属关系的可能的HAC。对所有25名候选者进行FVIII水平、活化部分凝血活酶时间（APTT）和出血风险评估，并对其FVIII基因的外显子14的一部分进行测序。
25%的参与者FVIII水平较低，但他们中没有人有出血时间延长或出血倾向。我们还在6名候选者中鉴定出两个错义变异，但这些变异的临床意义此前尚未确定。
这项初步研究首次探索了沙特阿拉伯若干HAC的表型。需要对更多的HA患者及其女性亲属进行更大规模的研究，以了解表型与基因型之间的相关性，从而更好地筛查HAC。
