Novel mutation in the ligand-binding domain of the androgen receptor gene （1790p） associated with complete androgen insensitivity syndrome

Mutations in the X-linked androgen receptor （AR） gene cause androgen insensitivity syndrome （AIS）, resulting in an impaired embryonic sex differentiation in 46,XY genetic men. Complete androgen insensitivity （CAIS） produces a female external phenotype, whereas cases with partial androgen insensitivity （PALS） have various ambiguities of the genitalia. Mild androgen insensitivity （MAIS） is characterized by undermasculinization and gynecomastia. Here we describe a 2-month-old 46,XY female patient, with all of the characteristics of CAIS. Defects in testosterone （T） and dihydrotestosterone （DHT） synthesis were excluded. Sequencing of the AR gene showed the presence in exon 6 of a T to C transition in the second base of codon 790, nucleotide position 2369, causing a novel missense Leu790Pro mutation in the ligand-binding domain of the AR protein. The identification of a novel AR mutation in a girl with CAIS provides significant information due to the importance of missense mutations in the ligand-binding domain of the AR, which are able to induce functional abnormalities in the androgen binding capability, stabilization of active conformation, or interaction with coactivators.

A novel nonsense mutation of GPR143 gene in a Korean kindred with X-linked congenital nystagmus

Dear Editor,I am Dr.Ungsoo Samuel Kim.from Kim＇s Eye Hospital,Konyang University,Seoul,Korea.I write to present a novel mutation of GPR143 in Korean patients with X-linked congenital nystagmus by using exome sequencing.Congenital nystagmus is an inherited ocular disorder that can occur as an X-linked condition.

Mutation in a novel gene SMALL AND CORDATELEAF 1 affects leaf morphology in cucumber

Plant species exhibit substantial variation in leaf morphology.VWe isolated a recessive mutant gene termed small and cordate leaf 1（sclh）that causes alteration in both leaf size and shape of cucumber.Compared to wild type leaves,the sclh mutant had fewer numbers of epidermal pavement cells.A single nucleotide polymorphism was associated with this leaf phenotype,which occurred in a putative nucleoside bisphosphate phosphatase.RNA-seq analysis of the wild type and sclh mutant leaves suggested that SCL;regulation may not involve known hormonal pathways.Our work identified a candidate gene for SCL;that may play a role in leaf development.

AR mutations in 28 patients with androgen insensitivity syndrome(Prader grade 0–3)

We investigated the androgen receptor(AR) gene mutation profiles of Chinese patients exhibiting severe androgen insensitivity syndrome(AIS) phenotypes. The present study enrolled 28 patients with genetically diagnosed AIS, who presented with severe phenotypes(Prader grade 0–3). Patients and some family members were screened via amplification and sequencing of their AR exons 1–8, including the corresponding intronic flanking regions. Luteinizing(LH), follicle-stimulating(FSH), and testosterone(T) hormone levels were found to be slightly, but not significantly, higher in patients with complete androgen insensitivity syndrome(CAIS) than in patients with partial androgen insensitivity syndrome(PAIS)(P>0.05). We identified 24 different AR mutations, including 12 that were novel. Ten patients(cases 2, 3, 10, 28, 11, 12, 19, 20, 24, and 25) were found to carry five recurrent mutations(p.Y572 S, p.P914 S, p.S176 R, p.Y782 N, and p.R841H); of these, p.Y572 S, p.S176 R, and p.Y782 N were novel. Among the mutations identified in patients with CAIS, six(66.7%) were characterized as single-nucleotide missense mutations, and six(66.7%) were found to be located in the AR ligand-binding domain(LBD). Among the mutations identified in patients with PAIS, 15(93.8%) were found to be missense, and 11(68.8%) were found to be located in the LBD. Patients 10 and 28 were determined to harbor the same missense mutation(p.P914S), but were diagnosed with CAIS and PAIS, respectively.Sex hormone levels were slightly, but not significantly, elevated in patients with CAIS compared to those with PAIS. Missense mutations spanning AR exons 1–8 were the predominant form of identified mutations, and these were mostly located in the AR LBD. Approximately 50% of the identified mutations were novel, and have enriched the AR gene-mutation database. Patients harboring identical mutations were in some instances found to exhibit divergent phenotypes.