Division of Pediatric Endocrinology, Department of Pediatrics, Medical School of Patras, University Hospital, Rio, Greece.
Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Eur J Hum Genet. 2022 Oct;30(10):1191-1194. doi: 10.1038/s41431-022-01076-z. Epub 2022 Mar 11.
The pituitary gland, as a nodal component of the endocrine system, is responsible for the regulation of growth, reproduction, metabolism, and homeostasis. Although pituitary formation though the hierarchical action of different transcription factors is well studied in mouse models, there is little evidence of the analogous developmental processes in humans. Herein, we present a female patient with a phenotype that includes blepharoptosis-ptosis-epicanthus syndrome and premature ovarian failure. Clinical exome sequencing revealed two heterozygous variants in two genes, LHX4 (pathogenic) and NR5A1 (VUS) genes and no mutation in FOXL2 gene. We propose a model of genetic interaction between LHX4 and NR5A1 during pituitary and ovarian development that may lead to a similar phenotype mediated by reduced FOXL2 expression.
垂体作为内分泌系统的一个节点组成部分，负责调节生长、生殖、代谢和内稳态。虽然通过不同转录因子的分层作用在小鼠模型中对垂体的形成进行了很好的研究，但在人类中几乎没有类似的发育过程的证据。在此，我们介绍了一位女性患者，其表型包括上睑下垂-上睑下垂-内眦赘皮综合征和卵巢早衰。临床外显子组测序显示两个基因 LHX4（致病性）和 NR5A1（意义未明变异）中的两个杂合变异，FOXL2 基因无突变。我们提出了一个 LHX4 和 NR5A1 在垂体和卵巢发育过程中遗传相互作用的模型，该模型可能导致 FOXL2 表达减少介导的类似表型。
