Homozygous nonsense mutation in SCHIP1/IQCJ-SCHIP1 causes a neurodevelopmental brain malformation syndrome.

We report a consanguineous Arab family with 3 affected siblings who display a disorder of global developmental delay, learning difficulties, facial dysmorphism, hearing impairments, and cataract. The clinical phenotype was associated with characteristic brain magnetic resonance imaging (MRI) features of axonal guidance defects involving anterior commissure agenesis as well as scattered areas of polymicrogyria-cobblestone complex. Whole genome sequencing revealed a novel nonsense mutation (159609921C>T) that segregated in the family consistent in an autosomal recessive pattern. This mutation located in the C-terminal region shared by the Schwanomin-Interacting Protein1 (SCHIP1) isoforms including the IQCJ-SCHIP1. The in vitro expression of SCHIP1 and IQCJ-SCHIP1 truncated mutant isoforms (NM_001197109.1; p.R209* and NM_001197114.1; p.R501*, respectively) were markedly reduced as compared to their full-length versions suggesting protein stability/folding impairment. The pathogenic nature of this mutation is supported by a previously reported mouse knockout of Schip1 isoforms, which phenocopied the human axon guidance abnormality. This is the first report of a SCHIP1/IQCJ-SCHIP1 point mutation in humans associated with a neurological-developmental phenotype.

An update on hepatic stem cells: bench to bedside.

Liver failure results in impairment of many functions and dependent organs such as brain and kidneys begin to fail, reducing the chance of recovery even further. Orthotopic liver transplantation (OLTx) is the only treatment that improves the survival rate in patients with liver failure. Liver Transplantation (LT), including orthologous liver transplantation (OLT), cadaveric LT, split LT, living donor LT (LDLT) brings hopes to patients with these diseases. Globally, 1.4 million deaths occur annually as a result of chronic liver diseases. The reasons for this high death toll include unavailability of healthy liver donor and highly expensive liver transplantation treatment. Furthermore, some other factors such as operative risks and post-transplant rejection are major limitation of OLT. Isolated hepatocyte transplantation is emerging as alternative bridge support till the healthy donor is arranged. Mature hepatocytes have several drawbacks such as low proliferation both in vitro and in vivo, low viability after cryopreservation, and requirement of large number of cells for infusion. The studies on isolation of hepatic progenitors have shown promising results to overcome these limitations. These cells possess higher proliferative capacity, are less immunogenic and more resistant to cryopreservation, and ischemic injury; properties that could enhance their engraftment within the recipient liver. The hepatic progenitors have been isolated from the intra-hepatic sources and extra-hepatic sources. Fetal cells are one of the ideal sources of hepatic stem/progenitor cells. Autologous bone marrow stem cell transplantation in patients with cirrhosis has shown promising result.

Chilblains as a diagnostic sign of aicardi-goutières syndrome.

Aicardi-Goutières syndrome (AGS) is a genetically heterogeneous disorder showing variability in age of onset and clinical features. Chilblain lesions have been described in AGS patients and recent papers have discussed the clinical, molecular and cutaneous histopathological overlap with chilblain lupus. Here we report on 2 unrelated children with AGS and chilblain lesions, whose clinical histories and examination findings well illustrate the wide phenotypic variability that can be seen in this pleiotropic disorder. Although both patients show remarkable similarity in the histopathology of their associated skin lesions, with thrombi formation, fat necrosis and hyalinization of the subcutaneous tissue, we note that the histopathology reported in other AGS cases with chilblains does not necessarily demonstrate this same uniformity. Our findings highlight the significant role of the characteristic chilblain skin lesions in the diagnosis of AGS, and variability in the associated histopathology which may relate to the stage and severity of the disease.

Stem cell therapy-present status.

Stem cell research is a new field that is advancing at an incredible pace with new discoveries being reported from all over the world. Scientists have for years looked for ways to use stem cells to replace cells and tissues that are damaged or diseased. Stem cells are the foundation cells for every organ, tissue, and cell in the body. Stem cells are undifferentiated, "blank" cells that do not yet have a specific function. Under proper conditions, stem cells begin to develop into specialized tissues and organs. They are self-sustaining and can replicate themselves for long periods of time. Embryonic stem cells are pluripotent cells, isolated from the inner cell mass of the blastocyst-stage mammalian embryo. They have the ability to differentiate into several somatic or somatic-like functional cells such as neurons, hepatocytes, cardiomyocytes, and others. Adult stem cells are specialized cells found within many tissues of the body where they function in tissue homeostasis and repair. They are precursor cells capable of differentiation into several different cells. The knowledge of stem cells from various sources offered a new hope for the treatment of various diseases.