ESPE Abstracts

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...

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...

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...

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...

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...

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:...

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:...

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...

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 ...

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: ...