Identification of a Novel Nonsense Homozygous Mutation of LINS1 Gene in Two Sisters With Moderate Intellectual Disability, Schizophrenia, and Anxiety Disorders and Review of the Literature

Background: The human LINS1 gene is located at 15q26.3 and encodes the lines homolog 1 protein that contains the Drosophila lines homologous domain. Mutations in the LINS1 gene have been reported to cause a rare recessive form of intellectual disability. A total of seven mutations in six studies have been reported in the literature to our knowledge. Results: Using whole genome sequencing analysis, we identified a novel homozygous nonsense mutation in the LINS1 gene in these two sisters who presented moderate intellectual disability, schizophrenia symptoms, and severe anxiety. The mutation was a C-to-T substitution at the cDNA nucleotide position 274 that changed the amino acid glutamine at the codon 92 to stop codon (Gln92X), resulting in the truncation of LINS1 protein after amino acid 91. This mutation was transmitted from their unrelated parents who were heterozygous carriers. Conclusions: Our findings not only add to the allelic heterogeneity of the LINS1-associated intellectual disability but also expand the spectrum of clinical phenotypes of patients with LINS1 mutations. Our study suggests that the human LINS1 gene mutation may play a role in the pathogenesis of psychosis and anxiety in addition to the intellectual disability.

Molecular Cloning and Characterization of PI3K-p85α Gene from Inner Mongolia Cashmere Goat (Capra hircus)

PI3K, phosphatidylinositol-3-kinase, is a specific lipid kinase family. It is associated with cell proliferation and survival..Class-IA PI3K is heterodimers composed of catalytic subunit (p110) and regulatory subunit (p85). p85α is the most abundant regulatory subunit of PI3K family. PI3K-p85α partial cDNA was amplified by RT-PCR from Inner Mongolia Cashmere Goat (Capra hircus) and sequenced. The molecular characterization of the PI3K-p85α gene was described. The amplified fragment is 1152bp in length, corresponding to a polypeptide of 384 amino acids residues with 45.4 kDa predicted molecular mass. The cDNA nucleotide sequence has 98% identity with regulatory subunit alpha (PIK3R1) of bovine and 93% identity with human. The goat PI3K-p85α patial cDNA is cloned.

A Standard Nomenclature for von Willebrand Factor Gene Mutations and Polymorphisms

SummaryExamination of the entire von Willebrand factor (VWF) gene for mutations, particularly in types 1 and 3 von Willebrand disease (VWD) is becoming more widely practised. The sequence of the entire VWF gene will soon be compiled as a single sequence. For these reasons, a clearly defined nomenclature to use for numbering the VWF nucleotide and amino acid sequence is required.The following recommendations are made for VWF numbering. VWF cDNA nucleotide sequence should be numbered from the A of the initiator ATG as the +1 position. Genomic DNA should be prefixed with a “g” and also numbered from this position. Amino acid (aa) numbering should be from the initiator methionine as the +1 position with sequential numbering of aa throughout VWF. To avoid confusion with previously used numbering schemes for mature VWF, which started from serine 764 of pre-pro VWF, the use of the single letter amino acid code is recommended.

Cathepsin P, a novel protease in mouse placenta

The complete cDNA nucleotide sequence of a novel cathepsin derived from mouse placenta, termed cathepsin P, was determined. mRNA for cathepsin P was expressed in placenta and at lower levels in visceral yolk sac, but could not be detected in a range of adult tissues. The expression pattern of this protease indicates that it probably plays an important role during implantation and fetal development.