hrp0084p3-993 | Gonads | ESPE2015

The Effect of Aromatase Inhibitor in a Pubertal Patient with Aromatase Excess Syndrome

Shihara Daziou , Sato Hidetoshi , Ogawa Yohei , Miyado Mami , Fukami Maki

Background: Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder caused by the overexpression of CYP19A1 at 15q21. Patients with AEXS manifest various clinical features associated with oestrogen excess; gynecomastia, hypogonadotropic hypogonadism, and advanced bone age are the most salient features in this condition.Objective and hypotheses: The primordial treatment of the gynecomastia in patients with AEXS is surgical mastecto...

hrp0082p2-d1-571 | Sex Development | ESPE2014

Identification of a Missense MAP3K1 Mutation in a Patient with Hypospadias

Igarashi Maki , Horikawa Reiko , Nakabayashi Kazuhiko , Hata Kenichirou , Ogata Tsutomu , Fukami Maki

Background: Recently, eight MAP3K1 mutations have been identified in patients with 46,XY disorder of sex development (DSD), although detailed clinical findings of the mutation-positive patients remain to be investigated.Objective and hypotheses: To clarify the frequency and clinical consequences of MAP3K1 mutations.Method: Mutation screening of MAP3K1 were performed for 37 patients with 46,XY DSD. Phenoty...

hrp0082p1-d3-98 | Sex Development | ESPE2014

A Novel NR5A1 Mutation with Preserved Fertility

Yagi Hiroko , Takagi Masaki , Hasegawa Yukihiro , Igarashi Maki , Kon Masafumi , Fukami Maki

Background: The common phenotype caused by NR5A1 mutations of 46,XY is gonadal dysgenesis without adrenal deficiency. Preserved fertility of the affected males was described in two patients with different mutations. No functional analysis of these two mutations has been done. Here we report brothers with isolated hypospadias who carries a novel heterozygous mutation of c.910G>A, E304K in NR5A1 gene. Their asymptomatic father carries the same nucleotide ch...

hrp0092fc3.1 | Multi-system Endocrine Disorders | ESPE2019

Germline-Derived Gain-of-Function Variants of Gsα-Coding GNAS Gene Identified in Nephrogenic Syndrome of Inappropriate Antidiuresis: The First Report

Fukami Maki , Miyado Mami , Takada Shuji , Sasaki Goro , Nagasaki Keisuke , Masunaga Youhei , Saitsu Hirotomo , Ogata Tsutomu

Background: The stimulatory G-protein α-subunit encoded by GNAS exons 1–13 (GNAS-Gsα) mediates signal transductions of multiple G-protein-coupled receptors including arginine vasopressin (AVP) receptor 2 (AVPR2). To date, various germline-derived loss-of-function variants of maternal and paternal origin have been found in pseudohypoparathyroidism type Ia and pseudopseudohypoparathyroidism respectively, and specific somatic gain...

hrp0092p1-140 | Sex Differentiation, Gonads and Gynaecology or Sex Endocrinology | ESPE2019

Methylation Status of X Inactivation-Escape Genes in Controls and Females with X Chromosome Rearrangements

Kawashima Sayaka , Matsubara Keiko , Toki Machiko , Kosaki Rika , Hasegawa Yukihiro , Fukami Maki , Kagami Masayo

Context: X chromosome inactivation (XCI) is a process in which one of the two X chromosomes in a female is randomly inactivated in order to correct gene dosage between males and females. However, about 15% of genes escape from XCI (termed escapees), and 10% of genes are variably inactivated (variable genes). The mechanism of inactivation and escape remains to be revealed. The promoter regions of escapees are hypomethylated compared to those of the inac...

hrp0089rfc3.4 | Diabetes and Insulin 1 | ESPE2018

Functional Characterization of a Novel KLF11 Mutation Identified in a Family with Autoantibody-Negative Type 1 Diabetes

Ushijima Kikumi , Kawamura Tomoyuki , Ogata Tsutomu , Yokota Ichiro , Sugihara Shigetaka , Narumi Satoshi , Fukami Maki

Objectives: KLF11 is a member of the Sp1/KLF family transcription factor which contains three C2H2 zinc finger domains. To date, two KLF11 mutations (p.T220M and p.A347S) have been identified in three families clinically diagnosed with type 2 diabetes. The aim of our study is to report clinical and molecular characteristics of a KLF11 mutation-carrying family clinically diagnosed with type 1 diabetes (T1D).Methods:...

hrp0089p2-p013 | Adrenals and HPA Axis P2 | ESPE2018

A First Combination Case of 21-Hydroxilase Deficiency and CHARGE Syndrome Confirmed by Genetic Analysis

Kitamura Miyuki , Katoh-Fukui Yuko , Fukami Maki , Yatsuga Shuichi , Matsumoto Takako , Nishioka Junko , Koga Yasutoshi

Introduction: 21-hydroxilase deficiency (21OHD) is the most common form of congenital adrenal hyperplasia. Mutations of CYP21A2 induces 21OHD, a rare autosomal recessive manner. CHARGE syndrome (CS) is a rare autosomal dominant manner that is typically caused by heterozygous chromodomain helicase DNA binding protein-7 (CHD7) mutations. Here, we report the combination cases with genetically diagnosing 21OHD and CS at the first time.Case:...

hrp0084p1-90 | Growth | ESPE2015

Silver-Russell Syndrome without Body Asymmetry in Three Patients with Duplications of Maternally Derived Chromosome 11p15 Involving CDKN1C

Nakashima Shinichi , Kato Fumiko , Kosho Tomoki , Nagasaki Keisuke , Kikuchi Toru , Kagami Masayo , Fukami Maki , Ogata Tsutomu

Background: Silver-Russell syndrome (SRS) is a congenital developmental disorder characterised by pre- and post-natal growth failure, relative macrocephaly, hemihypotrophy, and fifth-finger clinodactyly. Recent studies have shown that gain-of-function mutations of CDKN1C result in IMAGe syndrome (IMAGeS) characterized by intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and male genital abnormalities, whereas less severe gain-of-function mut...

hrp0092rfc12.3 | Growth and Syndromes (to include Turner syndrome) | ESPE2019

Imprinting Defects and Copy Number Variations in Short Children Born Small for Gestational Age

Kagami Masayo , Nakamura Akie , Inoue Takanobu , Kawashima Sayaka , Hara Kaori , Fuke Tomoko , Mastubara Keiko , Fukami Maki , Ogata Tsutomu

Abnormal expression of imprinted genes leads to imprinting disorders (IDs). Silver-Russell syndrome (SRS) and Prader-Willi syndrome (PWS) are representative IDs showing small for gestational age and short stature (SGA-SS).Temple syndrome (TS14) caused by abnormal gene expression at the 14q32.2 imprinted region, maternal uniparental disomy of chromosome 6 (UPD(6)mat), 16 (UPD(16)mat), and 20 (UPD(20)mat) are also associated with SGA-SS. Fuethermore, some copy number variations ...

hrp0086p1-p728 | Pituitary and Neuroendocrinology P1 | ESPE2016

FGFR1 Loss-of-Function Mutations of in Three Japanese Patients with Isolated Hypogonadotropic Hypogonadism and Split Hand/Foot Malformation

Ohtaka Kohnosuke , Yamaguchi Rie , Yagasaki Hideaki , Miyoshi Tatsuya , Hasegawa Hiroyuki , Hasegawa Tomonobu , Miyoshi Hideaki , Fukami Maki , Ogata Tsutomu

Background: Heterozygous loss-of-function mutations of FGFR1 are known to cause Kallmann syndrome (KS) and isolated hypogonadotropic hypogonadism (IHH). Furthermore, recent studies have also indicated that heterozygous loss-of-function mutations lead to IHH and split hand/foot malformation (SHFM).Objective and hypotheses: The objective of this study was to examine FGFR1 in three Japanese patients with IHH and SHFM.Method: ...