hrp0082p3-d2-971 | Sex Development (1) | ESPE2014

A Case of 46,Y,dup(x)(p21.2p22.2) DSD Caused by Overexpressed DAX1

Takako Sasaki , Youko Izumi , Maki Fukami , Shuichi Yatsuga , Yasutoshi Koga

Introduction: DAX1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) plays an important role in developing the adrenal gland and testis during embryonic stage. On the other hand, overexpressed DAX1 causes 46,XY disorders of sex development (DSD), in which patients often have short stature, mental retardation, and telecanthus. Here we report a case of 46,Y,dup(X)(p21.2p22.2) DSD caused by overexpressed DAX1.Case ...

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...

hrp0095p1-112 | Growth and Syndromes | ESPE2022

Long-term follow-up of aromatase-inhibitor use in 3 family members with aromatase excess syndrome

Giannopoulou Eleni , Brandt Stephanie , Schmidt Martin , Fukami Maki , Wabitsch Martin

Introduction: Aromatase excess syndrome (AEXS) is a rare, autosomal dominant disorder, characterized by enhanced extraglandular aromatization of androgens and estrogen excess. Genomic rearrangements in chromosome 15q21 are found to result in overexpression of the aromatase gene CYP19A1. In males it is characterized by pre- or peripubertal gynecomastia, hypogonadotropic hypogonadism, advanced bone age and short adult height. Only a few female patients have been...

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:...

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...

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...

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...