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.
authors: Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
authors: Yumi
authors: Y
authors: Asakura
authors: Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
authors: Koji
authors: K
authors: Muroya
authors: Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
authors: Junko
authors: J
authors: Hanakawa
authors: Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan ; Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors: Takeshi
authors: T
authors: Sato
authors: Department of Radiology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors: Noriko
authors: N
authors: Aida
authors: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors: Satoshi
authors: S
authors: Narumi
authors: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors: Tomonobu
authors: T
authors: Hasegawa
authors: Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
authors: Masanori
authors: M
authors: Adachi
keywords: PROK2; PROKR2; combined pituitary hormone deficiency (CPHD); morning glory syndrome; pituitary dysplasia