Two novel missense mutations in iron transport protein transferrin causing hypochromic microcytic anaemia and haemosiderosis: molecular characterization and structural implications

Transferrin (TF) is a monomeric glycoprotein that facilitates the transport of ferric iron (Fe(III)) between the sites of absorption, storage and utilization. Atransferrinaemia or hypotransferrinaemia is an extremely rare autosomal recessive disease (OMIM#209300, ORPHA1195) characterized by severe deficiency of serum TF, the ligand for TF receptor which enables cellular iron uptake into various tissues. To date, only 14 cases have been reported, half of which have been character- ized at the molecular level (Beutler et al, 2000; Chen et al, 2009). In this report we describe two novel missense mutations D647V and R609W (Uniprot: TRFE_HUMAN; P02787) in the transferrin gene (TF) found in two patients from two Indian non-consanguineous families.This study was supported in part by a grant BT/PR-13968/MED/12/465/2010 from the Department of Biotechnology, Government of India to ES and by the grant SAF2012-40106 from the Spanish Secretary of Research, Development and Innovation (MINECO) and the grant CIVP16A1857 “Ayudas a proyectos de Investigación en Ciencias de la Vida- Fundación Ramón Areces” to M.S. M.S. held a research contract under the Ramón y Cajal program from the Spanish Ministry of Science and Innovation (RYC-2008-02352).Peer reviewe

A novel splice site mutation c.2278 (-1) G>C in the TMPRSS6 gene causes deletion of the substrate binding site of the serine protease resulting in refractory iron deficiency anaemia

This article does not have an abstract

Meconium Ileus due to GUCY2C gene mutations in three unrelated South Indian families

Meconium ileus (MI) typically occurs in infants subsequently diagnosed with cystic fibrosis (CF). Apart from prematurity and anecdotal case reports of congenital malformations of the gut and pancreas, the only other pathophysiological cause of MI is the recently described homozygous loss of function mutations in the GUCY2C gene. GUCY2C gene mutations causing MI were first identified in Israeli Bedouin kindred and subsequently in a Lebanese family [1,2]. The gene encodes for a trans-membrane protein called guanylate cyclase 2C. The protein is expressed in the intestinal epithelium where it is an activator of the cystic fibrosis transmembrane conductance regulator (CFTR). We report three further cases of MI in families in South India, homozygous for GUCY 2C gene variants