Congenital hypopituitarism due to novel compound heterozygous POU1F1 gene mutation: A case report and review of the literature

Wei-Yu Chen; Dau-Ming Niu; Li-Zhen Chen; Chia-Feng Yang

doi:10.1016/j.ymgmr.2021.100819

Congenital hypopituitarism due to novel compound heterozygous POU1F1 gene mutation: A case report and review of the literature

Mol Genet Metab Rep. 2021 Nov 12:29:100819. doi: 10.1016/j.ymgmr.2021.100819. eCollection 2021 Dec.

Authors

Wei-Yu Chen^{1

2

3}, Dau-Ming Niu^{1

2

3}, Li-Zhen Chen³, Chia-Feng Yang^{1

2

3}

Affiliations

¹ School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
² School of Medicine, National Yang-Ming University, Taipei, Taiwan.
³ Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.

Abstract

Failure to thrive is one of the most common complaints in the endocrinology and genetics clinic. An 8-month-old girl with presentation of motor developmental delay, failure to thrive, and midline facial defects, with history of hypoglycemia at birth and central congenital hypothyroidism (CCH), was brought to our genetic clinic. Hormone test demonstrated combined pituitary hormone deficiency with growth hormone deficiency (GHD), central hypothyroidism, and hypoprolactinemia. Brain magnetic resonance imaging (MRI) showed anterior pituitary hypoplasia (APH), abnormal pituitary stalk, and preserved posterior pituitary lobe. Whole exome sequence (WES) identified a compound heterozygous mutation of the POU1F1 gene: c.649C>T (p.Arg217Ter) and c.662T>C (p.Ile221Thr), which are de novo mutation and inherited from mother, respectively. The patient's phenotype was consistent clinically with congenital hypopituitarism due to the POU1F1 gene mutation. Based on our literature review, this is the first report of the c.662T>C mutation, to the best of our knowledge. Our study demonstrates the power of WES for early diagnosis of congenital hypopituitarism with its relative phenotype for improving prognosis and preventing irreversible deficit.

Keywords: APH, Anterior pituitary hypoplasia; CCH, Central congenital hypothyroidism; Failure to thrive; GHD, Growth hormone deficiency; MRI, Magnetic resonance imaging; Midline facial defect; POU1F1 mutation; TVGH, Taipei Veterans General Hospital; WES, Whole exome sequence; Whole exome sequence.