Combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous PROKR2 mutation

Yumi Asakura, Koji Muroya, Junko Hanakawa, Takeshi Sato, Noriko Aida, Satoshi Narumi, Tomonobu Hasegawa, Masanori Adachi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of congenital hypopituitarism, including septo-optic dysplasia and Kallmann syndrome. In the present study, using next-generation targeted sequencing, we identified a novel heterozygous PROKR2 variant (c.742C>T; p.R248W) in a female patient who had combined pituitary hormone deficiency (CPHD), morning glory syndrome and a severely malformed pituitary gland. No other mutation was present in 27 genes related to hypogonadotropic hypogonadism, pituitary hormone deficiency and optic nerve malformation. The substituted amino acid was located on the third intracellular loop of the PROKR2 protein, which is a G protein-coupled receptor. Computational analyses with two programs (SIFT and PolyPhen-2) showed that the substitution was deleterious to PROKR2 function. The p.R248W mutation was transmitted from the patient’s mother, who had a slightly delayed menarche. Collectively, we provide further genetic evidence linking heterozygous PROKR2 mutations and the development of CPHD.

Original languageEnglish
Pages (from-to)27-32
Number of pages6
JournalClinical Pediatric Endocrinology
Volume24
Issue number1
DOIs
Publication statusPublished - 2015

Fingerprint

Mutation
Genes
Septo-Optic Dysplasia
Kallmann Syndrome
Hypopituitarism
Menarche
Hypogonadism
Pituitary Hormones
Pituitary Gland
Optic Nerve
G-Protein-Coupled Receptors
Mothers
Combined Pituitary Hormone Deficiency
Amino Acids
Proteins

Keywords

  • Combined pituitary hormone deficiency (CPHD)
  • Morning glory syndrome
  • Pituitary dysplasia
  • PROK2
  • PROKR2

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Pediatrics, Perinatology, and Child Health

Cite this

Combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous PROKR2 mutation. / Asakura, Yumi; Muroya, Koji; Hanakawa, Junko; Sato, Takeshi; Aida, Noriko; Narumi, Satoshi; Hasegawa, Tomonobu; Adachi, Masanori.

In: Clinical Pediatric Endocrinology, Vol. 24, No. 1, 2015, p. 27-32.

Research output: Contribution to journalArticle

Asakura, Yumi ; Muroya, Koji ; Hanakawa, Junko ; Sato, Takeshi ; Aida, Noriko ; Narumi, Satoshi ; Hasegawa, Tomonobu ; Adachi, Masanori. / Combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous PROKR2 mutation. In: Clinical Pediatric Endocrinology. 2015 ; Vol. 24, No. 1. pp. 27-32.
@article{e8cb4ecfd0f349b8bc90592487e43e87,
title = "Combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous PROKR2 mutation",
abstract = "Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of congenital hypopituitarism, including septo-optic dysplasia and Kallmann syndrome. In the present study, using next-generation targeted sequencing, we identified a novel heterozygous PROKR2 variant (c.742C>T; p.R248W) in a female patient who had combined pituitary hormone deficiency (CPHD), morning glory syndrome and a severely malformed pituitary gland. No other mutation was present in 27 genes related to hypogonadotropic hypogonadism, pituitary hormone deficiency and optic nerve malformation. The substituted amino acid was located on the third intracellular loop of the PROKR2 protein, which is a G protein-coupled receptor. Computational analyses with two programs (SIFT and PolyPhen-2) showed that the substitution was deleterious to PROKR2 function. The p.R248W mutation was transmitted from the patient’s mother, who had a slightly delayed menarche. Collectively, we provide further genetic evidence linking heterozygous PROKR2 mutations and the development of CPHD.",
keywords = "Combined pituitary hormone deficiency (CPHD), Morning glory syndrome, Pituitary dysplasia, PROK2, PROKR2",
author = "Yumi Asakura and Koji Muroya and Junko Hanakawa and Takeshi Sato and Noriko Aida and Satoshi Narumi and Tomonobu Hasegawa and Masanori Adachi",
year = "2015",
doi = "10.1297/cpe.24.27",
language = "English",
volume = "24",
pages = "27--32",
journal = "Clinical Pediatric Endocrinology",
issn = "0918-5739",
publisher = "Jeff Corporation Co. Ltd",
number = "1",

}

TY - JOUR

T1 - Combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous PROKR2 mutation

AU - Asakura, Yumi

AU - Muroya, Koji

AU - Hanakawa, Junko

AU - Sato, Takeshi

AU - Aida, Noriko

AU - Narumi, Satoshi

AU - Hasegawa, Tomonobu

AU - Adachi, Masanori

PY - 2015

Y1 - 2015

N2 - Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of congenital hypopituitarism, including septo-optic dysplasia and Kallmann syndrome. In the present study, using next-generation targeted sequencing, we identified a novel heterozygous PROKR2 variant (c.742C>T; p.R248W) in a female patient who had combined pituitary hormone deficiency (CPHD), morning glory syndrome and a severely malformed pituitary gland. No other mutation was present in 27 genes related to hypogonadotropic hypogonadism, pituitary hormone deficiency and optic nerve malformation. The substituted amino acid was located on the third intracellular loop of the PROKR2 protein, which is a G protein-coupled receptor. Computational analyses with two programs (SIFT and PolyPhen-2) showed that the substitution was deleterious to PROKR2 function. The p.R248W mutation was transmitted from the patient’s mother, who had a slightly delayed menarche. Collectively, we provide further genetic evidence linking heterozygous PROKR2 mutations and the development of CPHD.

AB - Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of congenital hypopituitarism, including septo-optic dysplasia and Kallmann syndrome. In the present study, using next-generation targeted sequencing, we identified a novel heterozygous PROKR2 variant (c.742C>T; p.R248W) in a female patient who had combined pituitary hormone deficiency (CPHD), morning glory syndrome and a severely malformed pituitary gland. No other mutation was present in 27 genes related to hypogonadotropic hypogonadism, pituitary hormone deficiency and optic nerve malformation. The substituted amino acid was located on the third intracellular loop of the PROKR2 protein, which is a G protein-coupled receptor. Computational analyses with two programs (SIFT and PolyPhen-2) showed that the substitution was deleterious to PROKR2 function. The p.R248W mutation was transmitted from the patient’s mother, who had a slightly delayed menarche. Collectively, we provide further genetic evidence linking heterozygous PROKR2 mutations and the development of CPHD.

KW - Combined pituitary hormone deficiency (CPHD)

KW - Morning glory syndrome

KW - Pituitary dysplasia

KW - PROK2

KW - PROKR2

UR - http://www.scopus.com/inward/record.url?scp=84922453808&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922453808&partnerID=8YFLogxK

U2 - 10.1297/cpe.24.27

DO - 10.1297/cpe.24.27

M3 - Article

VL - 24

SP - 27

EP - 32

JO - Clinical Pediatric Endocrinology

JF - Clinical Pediatric Endocrinology

SN - 0918-5739

IS - 1

ER -