下丘脑/垂体后叶发育异常似乎是垂体柄中断综合征(PSIS)的主要决定因素。家族性病例和相关的先天性异常的观察表明遗传基础。单基因突变可以解释不到5%的病例,和整个外显子组测序显示出异质性的结果。本研究旨在使用基于阵列的比较基因组杂交(aCGH)评估非综合征性PSIS患者的拷贝数变异(CNV),并全面回顾来自先天性垂体功能减退症(CH)患者CNV分析文献的数据。来自我们门诊诊所的21例散发性CH患者表现为垂体后叶异位(EPP),磁共振图像(MRI)上无中枢神经系统异常或在体检时无任何其他畸形。在我们的患者中使用全基因组定制的400K寡核苷酸平台进行了aCGH。对于文献综述,我们检索了截至2021年11月在PubMed中通过核型或aCGH检测到的CH和CNV患者的病例报告.在18例患者(86%)中观察到35种不同的罕见CNV,其中2例(6%)被归类为致病性:17号染色体中1例缺失1.8Mb(17q12),18号染色体中1例缺失15Mb(18p11.32p11.21),每个人都在一个不同的病人身上。在文献综述中,在83例CH患者中发表了67例致病性CNVs,包括本研究。这些患者中的大多数患有EPP(鞍区MRI评估的45例中有78%),并且是综合征(70%)。最常受影响的染色体是X,18、20和1。我们的研究发现,CNV可能是非综合征性CH和EPP患者遗传异常的机制。在未来的研究中,这些CNVs中的一个或多个基因,致病性和不确定意义的变异,可以被认为是很好的候选基因。
Abnormal hypothalamic/posterior pituitary development appears to be a major determinant of pituitary stalk interruption syndrome (PSIS). The observation of familial cases and associated congenital abnormalities suggests a genetic basis. Single-gene mutations explain less than 5% of the cases, and whole exome sequencing has shown heterogeneous results. The present study aimed to assess copy number variation (CNV) using array-based comparative genomic hybridization (aCGH) in patients with non-syndromic PSIS and comprehensively
review data from the literature on CNV analysis in congenital hypopituitarism (CH) patients. Twenty-one patients with sporadic CH from our outpatient clinics presented with ectopic posterior pituitary (EPP) and no central nervous system abnormalities on magnetic resonance image (MRI) or any other malformations on physical examination at presentation were enrolled in the study. aCGH using a whole-genome customized 400K oligonucleotide platform was performed in our patients. For the literature
review, we searched for case reports of patients with CH and CNV detected by either karyotype or aCGH reported in PubMed up to November 2021. Thirty-five distinct rare CNVs were observed in 18 patients (86%) and two of them (6%) were classified as pathogenic: one deletion of 1.8 Mb in chromosome 17 (17q12) and one deletion of 15 Mb in chromosome 18 (18p11.32p11.21), each one in a distinct patient. In the literature
review, 67 pathogenic CNVs were published in 83 patients with CH, including the present study. Most of these patients had EPP (78% out of the 45 evaluated by sellar MRI) and were syndromic (70%). The most frequently affected chromosomes were X, 18, 20 and 1. Our study has found that CNV can be a mechanism of genetic abnormality in non-syndromic patients with CH and EPP. In future studies, one or more genes in those CNVs, both pathogenic and variant of uncertain significance, may be considered as good candidate genes.