Department of Cytogenetics, ICMR-National Institute of Immunohematology, 13th floor, New Multistoried Building, K.E.M. Hospital Campus, Mumbai, Maharashtra, 400012, India.
Department of Hematology, Institute of Child Health and Hospital for Children, Egmore, Chennai, Tamil Nadu, India.
Mol Biol Rep. 2021 Jan;48(1):585-593. doi: 10.1007/s11033-020-06101-2. Epub 2021 Jan 4.
Fanconi Anemia (FA) is a rare genetic disease with the incidence of 1 in 360,000 and is characterised by bone marrow failure, physical abnormalities, pancytopenia, and high frequency of chromosomal breakage and increased risk of evolving into malignancy. Telomere plays an important role in genomic stability, ageing process and cancers. Telomere shortening has been reported in FA. We studied telomere length in FA subjects and compared with complementation groups. Chromosomal breakage analysis from PHA stimulated, MMC induced peripheral blood culture was carried out in 37 clinically diagnosed FA. Molecular study of FANCA, G, and L was done through Sanger sequencing and next generation sequencing. Telomere length was estimated using real time quantitative polymerase chain reaction (qPCR) method. Student t-test was applied to test the significance. A high frequency of chromosomal breakage was observed in all the patients compared to healthy controls. We found significantly shorter telomere length in all the three complementation groups compare to age matched healthy controls. Among all complementation groups, FANCL showed severe telomere shortening (P value 0.0001). A negative correlation was observed between telomere length and chromosomal breakage frequency (R = -0.3116). Telomere shortening is not uncommon in FA subjects. However the telomere length shortening is different in complementation groups as FANCL showed severe telomere shortening in FA subjects. Though BM transplantation is essential for the management of the FA subjects, the telomere length can be considered as biological marker to understand the prognosis of the disease as FA subjects primarily treated with androgens.
范可尼贫血症（FA）是一种罕见的遗传性疾病，发病率为 1/360000，其特征是骨髓衰竭、身体异常、全血细胞减少症以及染色体断裂的高频发生和恶性肿瘤转化风险增加。端粒在基因组稳定性、衰老过程和癌症中发挥重要作用。已有研究报道 FA 中端粒缩短。我们研究了 FA 患者的端粒长度，并与互补群进行了比较。对 37 例临床诊断为 FA 的患者进行了 PHA 刺激、MMC 诱导外周血培养的染色体断裂分析。通过 Sanger 测序和下一代测序对 FANCA、G 和 L 进行了分子研究。使用实时定量聚合酶链反应（qPCR）方法估计端粒长度。应用学生 t 检验测试显著性。与健康对照相比，所有患者均观察到染色体断裂的高频发生。我们发现所有三个互补群的端粒长度均明显短于年龄匹配的健康对照组。在所有互补群中，FANCL 表现出严重的端粒缩短（P 值 0.0001）。观察到端粒长度与染色体断裂频率之间存在负相关（R = -0.3116）。FA 患者中端粒缩短并不罕见。然而，在互补群中，端粒长度缩短情况不同，因为 FANCL 在 FA 患者中表现出严重的端粒缩短。尽管骨髓移植是 FA 患者管理的重要手段，但端粒长度可作为生物标志物，用于了解疾病的预后，因为 FA 患者主要接受雄激素治疗。
