Hypergonadotropic Hypogonadism and Hypersegmented Neutrophils in a Patient with Ataxia-Telangiectasia-Like Disorder: Potential Diagnostic Clues?
Hypergonadotropic Hypogonadism and Hypersegmented Neutrophils in a Patient with Ataxia-Telangiectasia-Like Disorder: Potential Diagnostic Clues?
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共济失调毛细血管扩张样疾病患者的高促性腺激素性性腺功能减退症和中性粒细胞分叶过多：潜在的诊断线索？
DOI：
10.1002/ajmg.a.36546
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发表时间：
2014
期刊：
影响因子：
2
通讯作者：
et al.
中科院分区：
文献类型：
--
作者：
Yoshida T;Kobayashi J;et al.
共济失调-毛细血管扩张样疾病（ATLD）是一种罕见的常染色体隐性遗传病，其症状与共济失调-毛细血管扩张（AT）相似。ATLD是由参与DNA双链断裂修复（DSBR）的themre11基因突变引起的。与AT相比，ATLD患者缺乏关键的临床特征，如毛细血管扩张或免疫缺陷，因此难以诊断。我们报告一名女性ATLD患者，表现为促性腺功能亢进和嗜中性粒细胞过节段性，先前未描述该疾病的特征，以及将ATLD与其他疾病区分开来的潜在诊断线索。患者自2岁起表现为缓慢进行性小脑共济失调，MRI示小脑萎缩、动眼性失用症、轻度认知障碍、书写障碍、促性腺功能亢进伴原发性闭经、嗜中性粒细胞过节段。Western blot检测显示MRE11的完全缺失和ATM依赖性磷酸化的减少；因此，我们诊断为ATLD。遗传上，在themre11基因中检测到一种新的错义突变（c.140C>T），但在患者中未发现其他突变。我们的病人提示DSBR受损可能与促性腺功能亢进和中性粒细胞过度分割有关。综上所述，在评估原因不明的共济失调患者时，应考虑ATLD，并评估性腺状态和外周血涂片样本。©2014 Wiley期刊公司
Ataxia‐telangiectasia‐like disorder (ATLD) is a rare autosomal recessive disorder, and has symptoms similar to ataxia‐telangiectasia (AT). ATLD is caused by mutations in theMRE11gene, involved in DNA double‐strand break repair (DSBR). In contrast to AT, ATLD patients lack key clinical features, such as telangiectasia or immunodeficiency, and are therefore difficult to be diagnosed. We report a female ATLD patient presenting with hypergonadotropic hypogonadism and hypersegmented neutrophils, previously undescribed features in this disorder, and potential diagnostic clues to differentiate ATLD from other conditions. The patient showed slowly progressive cerebellar ataxia from 2 years of age, and MRI revealed atrophy of the cerebellum, oculomotor apraxia, mild cognitive impairment, writing dystonia, hypergonadotropic hypogonadism with primary amenorrhea, and hypersegmented neutrophils. Western blot assay demonstrated total loss of MRE11 and reduction of ATM‐dependent phosphorylation; thus, we diagnosed ATLD. Genetically, a novel missense mutation (c.140C>T) was detected in theMRE11gene, but no other mutation was found in the patient. Our presenting patient suggests that impaired DSBR may be associated with hypergonadotropic hypogonadism and neutrophil hypersegmentation. In conclusion, when assessing patients with ataxia of unknown cause, ATLD should be considered, and the gonadal state and peripheral blood smear samples evaluated. © 2014 Wiley Periodicals, Inc.