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首页> 外文期刊>The journal of clinical endocrinology and metabolism >Mutation and Gene Copy Number Analyses of Six Pituitary Transcription Factor Genes in 71 Patients with Combined Pituitary Hormone Deficiency: Identification of a Single Patient with LHX4 Deletion
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Mutation and Gene Copy Number Analyses of Six Pituitary Transcription Factor Genes in 71 Patients with Combined Pituitary Hormone Deficiency: Identification of a Single Patient with LHX4 Deletion

机译：71例垂体激素缺乏综合症患者6个垂体转录因子基因的突变和基因拷贝数分析：单例LHX4缺失患者的鉴定

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Context: Mutations of multiple transcription factor genes involved in pituitary development have been identified in a minor portion of patients with combined pituitary hormone deficiency (CPHD). However, copy number aberrations involving such genes have been poorly investigated in patients with CPHD.Objective: We aimed to report the results of mutation and gene copy number analyses in patients with CPHD.Subjects and Methods: Seventy-one Japanese patients with CPHD were examined for mutations and gene copy number aberrations affecting POU1F1 , PROP1 , HESX1 , LHX3 , LHX4 , and SOX3 by PCR-direct sequencing and multiplex ligation-dependent probe amplification. When a deletion was indicated, it was further studied by fluorescence in situ hybridization, oligoarray comparative genomic hybridization, and serial sequencing for long PCR products encompassing the deletion junction.Results: We identified a de novo heterozygous 522,009-bp deletion involving LHX4 in a patient with CPHD (GH, TSH, PRL, LH, and FSH deficiencies), anterior pituitary hypoplasia, ectopic posterior pituitary, and underdeveloped sella turcica. We also identified five novel heterozygous missense substitutions (p.V201I and p.H387P in LHX4 , p.T63M and p.A322T in LHX3 , and p.V53L in SOX3 ) that were assessed as rare variants by sequencing analyses for control subjects and available parents and by functional studies and in silico analyses.Conclusions: The results imply the rarity of abnormalities affecting the six genes in patients with CPHD and the significance of the gene copy number analysis in such patients.
机译：背景：垂体发育中涉及多种转录因子基因的突变已在少数合并垂体激素缺乏症（CPHD）的患者中得到鉴定。然而，CPHD患者中涉及此类基因的拷贝数畸变研究很少。目的：我们旨在报告CPHD患者的突变和基因拷贝数分析结果。研究对象和方法：检查了71名日本CPHD患者通过PCR直接测序和多重连接依赖探针扩增技术检测影响POU1F1，PROP1，HESX1，LHX3，LHX4和SOX3的突变和基因拷贝数异常。当发现缺失时，通过荧光原位杂交，寡阵列比较基因组杂交和包含缺失连接点的长PCR产物的序列测序进一步研究。结果：我们在患者中鉴定出涉及LHX4的从头杂合522,009-bp缺失CPHD（GH，TSH，PRL，LH和FSH缺乏），垂体前叶发育不全，异位后垂体和蝶鞍发育不良。我们还确定了5个新的杂合错义替换（LHX4中的p.V201I和p.H387P，LHX3中的p.T63M和p.A322T以及SOX3中的p.V53L）被测序对照受试者评估为罕见变异。结论：结果暗示异常罕见地影响了CPHD患者的六个基因，并且暗示了此类患者中基因拷贝数分析的重要性。

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