NBPF9 Gene May Be Involved in Congenital Hypopituitarism: A Whole-Genome Study of a Boy with Pituitary Stalk Interruption Syndrome and His Family.

Cheng-Zhi Wang,Ling-Ling Guo,Qing-Hua Guo,Yi-Ming Mu

doi:10.1155/2020/5401738

Abstract

Pituitary stalk interruption syndrome (PSIS) is a rare congenital defect manifesting as various degrees of anterior pituitary hormone deficiency. Scattered familial cases have been found, revealing some genetic variants. However, most of the previous research studies involved an affected sibling, and the gene spectra of the patients' entire family have rarely been reported. We conducted a study of a family consisting of a PSIS patient with his unaffected sibling and healthy parents of Han Chinese background using whole-genome sequencing. Bioinformatic analysis was carried out, and mutations related to PSIS, single-nucleotide variants (SNVs), insertion-deletion (InDELs), and structural variations (SVs) in all the four samples were filtered. After Sanger sequencing, we confirmed the variants obtained and selected three candidate genes for functional verification. The gene variations in this boy with PSIS and his lineal relatives are reported herein; de novo sequencing revealed that the NBPF9 gene may be involved in the pathogenesis of PSIS.

Highlights

Pituitary stalk interruption syndrome (PSIS) is a rare congenital defect with an estimated incidence of 0.5/100,000 births
He was born in a nonconsanguineous family, and none of his relatives had a history of growth retardation or short stature
We evaluate a family with a PSIS boy and a healthy sibling and parents, which may reveal more details of the etiology of PSIS

Summary

Introduction

Pituitary stalk interruption syndrome (PSIS) is a rare congenital defect with an estimated incidence of 0.5/100,000 births. PSIS causes various symptoms of pituitary hormone deficiency, including growth retardation and infertility [1,2,3]. Previous studies have revealed that genetic changes may contribute to its etiology. Studies on patients born to consanguineous parents have revealed germline mutations in some genes that may be responsible for the disease. Fernandez-Rodriguez et al reported a homozygous mutation, 301-302delAG, in the PROP1 gene in two consanguineous sisters [4]. Tatsi et al [5] found a novel heterozygous nonsense mutation (c.799C > T, p.Q267X) in the TGIF gene in a female PSIS patient with a single central incisor; her father had the same mutation but was asymptomatic

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