先天性角化不良患者的新发TINF2 C.845G>A致病变异

IF 0.5 4区 医学 Q4 GENETICS & HEREDITY
Balkan Journal of Medical Genetics Pub Date : 2022-06-05 eCollection Date: 2021-11-01 DOI:10.2478/bjmg-2021-0027
S A Kocheva, M Gjorgjievska, K Martinova, Z Antevska-Trajkova, A Jovanovska, D Plaseska-Karanfilska
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引用次数: 0

摘要

先天性角化不良(DC)是一种临床和遗传异质性的多系统遗传综合征,具有非常高的骨髓衰竭(BMF)和癌症易感性。DC的典型临床表现为皮肤色素沉着异常、指甲营养不良和口腔白斑。骨髓衰竭被认为是DC的重要和主要并发症,也是导致死亡的主要原因,约85%的病例会发生骨髓衰竭。许多参与端粒维持的基因与DC相关,例如编码端粒酶复合物(TERT, DKC1, TERC, NOP10和NHP2), t环组装蛋白(RTEL1),端粒盖层(CTC1),端粒保护蛋白复合物(TINF2)和端粒酶运输蛋白(TCAB1)成分的基因。据报道,11-20%的DC患者存在TINF2突变,并与骨髓衰竭有关。在这里,我们报告一个19个月大的男孩,很早就出现骨髓衰竭作为DC的第一个临床表现。首次入院时,患者表现为血小板减少症和大细胞性贫血。不久之后,他的血细胞计数随着全血细胞减少症和再生障碍性贫血的发展而恶化。4个月后出现指甲营养不良和皮肤色素沉着。通过临床外显子组测序,在TINF2基因6外显子中发现了一种新的杂合致病变异c.845G>A, p.(Arg282His)。结果证实了DC的诊断。这是北马其顿报告的第一例由TINF2致病性变异引起的DC病例。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

<i>de Novo TINF2</i> C.845G>A: Pathogenic Variant in Patient with Dyskeratosis Congenita.

<i>de Novo TINF2</i> C.845G>A: Pathogenic Variant in Patient with Dyskeratosis Congenita.

de Novo TINF2 C.845G>A: Pathogenic Variant in Patient with Dyskeratosis Congenita.

Dyskeratosis congenita (DC) is a clinically and genetically heterogeneous, multisystem inherited syndrome with a very high risk for bone marrow failure (BMF) and cancer predisposition. The classical clinical form of DC is characterized by abnormal skin pigmentation, nail dystrophy, and oral leukoplakia. Bone marrow failure is considered to be an important and major complication of DC and the leading cause of death which develops in around 85% of cases. A number of genes involved in telomere maintenance are associated with DC, such as genes that encode the components of the telomerase complex (TERT, DKC1, TERC, NOP10, and NHP2), T-loop assembly protein (RTEL1), telomere capping (CTC1), telomere shelterin complex (TINF2), and telomerase trafficking protein (TCAB1). Mutations in TINF2 have been reported in 11-20% of all patients with DC and have been associated with bone marrow failure. Here we report on a 19-month old boy with very early presentation of bone marrow failure as a first clinical manifestation of DC. Upon first admission, the patient presented with thrombocytopenia and macrocytic anemia. Soon after, his blood counts deteriorated with the development of pancytopenia and aplastic anemia. Four months later, he developed nail dystrophy and skin hyperpigmentation. A de novo heterozygous pathogenic variant c.845G>A, p.(Arg282His) was located in exon 6 of TINF2 gene and was identified via clinical exome sequencing. The findings confirmed the diagnosis of DC. This is the first case with DC due to TINF2 pathogenic variant reported in North Macedonia.

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来源期刊
CiteScore
1.00
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: Balkan Journal of Medical Genetics is a journal in the English language for publication of articles involving all branches of medical genetics: human cytogenetics, molecular genetics, clinical genetics, immunogenetics, oncogenetics, pharmacogenetics, population genetics, genetic screening and diagnosis of monogenic and polygenic diseases, prenatal and preimplantation genetic diagnosis, genetic counselling, advances in treatment and prevention.
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