ESPE Abstracts

Background: While hemizygous NR0B1 (DAX1) mutations usually lead to adrenal crisis during infancy or early childhood, p.Gln37*, p.Trp39*, and some other mutations result in late-onset or latent adrenal insufficiency. A small percentage of boys with NR0B1 mutations develops precocious puberty in addition to adrenal insufficiency.Objective and hypotheses: To report a boy with an NR0B1 mutation who exhibited central precocious puberty without adren...

Background: WDR11 has recently been reported as one of the causative genes of hypogonadotropic hypogonadism (HH). To date, five missense mutations in WDR11 have been identified in six patients with normosmic isolated HH (nIHH) or Kallmann syndrome (KS).Methods: We performed mutation screening of WDR11 for 46 cases with various types of HH. RT-PCR was carried out for a patient with a mutation. The protein structure of the mutant...

Context: Pseudohypoparathyroidism type 1B (PHP1B) caused by methylation defects of differentially methylated regions (DMRs) on the GNAS locus can be categorized into groups according to etiologies and methylation defect patterns of the DMRs. However, there are no reports evaluating the clinical differences in detail, such as diagnostic features at onset and Albright’s hereditary osteodystrophy (AHO) features, among the groups.<stro...

Background: Silver-Russell syndrome (SRS) is a rare congenital developmental disorder characterised by pre- and postnatal growth failure, relative macrocephaly, triangular face, hemihypotrophy, and fifth finger clinodactyly. Hypomethylation of the H19-DMR and maternal uniparental disomy chromosome 7 (UPD(7)mat) were identified in about 30 and 10% of SRS patients respectively. Genetic causes of the remaining 60% of the patients are unknown. Growth failure, small hands, and hypo...

Loss of methylation (LOM) at GNAS-A/B:TSS-differentially methylated regions (DMRs) in the GNAS locus is observed in pseudohypoparathyroidism type 1B (PHP1B). Many PHP1B cases are sporadic, but autosomal dominant-PHP1B has a deletion involving NESP55 expressed from the maternal allele or STX16 located upstream of the GNAS locus on the maternal allele. We report the possible first familial PHP1B cases with retrotransposon insertion in the GNAS locus on the maternal allele. To ou...