A translation frameshift mutation induced by a cytosine insertion in the polycystic kidney disease 2 gene (PDK2)

Mutations in the PKD2 gene on the long arm of chromosome 4 are responsible for approximately 15% of cases of polycystic kidney disease. Perhaps the only difference from the more common ADPKD1 cases is the rate of progression of cystic changes, and the age of onset, which is 10-15 years later for the ADPKD2 form. In Cyprus there are at least three large families, documented by molecular linkage analysis, that map to the PKD2 locus. For two of them the defects were recently shown to be nonsense mutations at positions arginine 742 and glutamine 405. In this report, we describe the mutation in the third family, CY1602. For this, the entire coding sequence was systematically screened by single strand conformation analysis and heteroduplex formation. A novel mutation was identified in exon 2 where a new cytosine residue was inserted immediately after codon 231 (231insC). It causes a translation frameshift and is expected to lead to the introduction of 37 novel amino acids before the translation reaches a new STOP codon. It is the most amino terminal mutation reported to date, and based on the protein's modeled structure, is predicted to be within the first transmembrane domain. It is the fourth PKD2 mutation reported thus far, and the first which is not a nonsense mutation.      

Determinants and consequences of short birth interval in rural Bangladesh: a cross-sectional study

Ethiopia is among seven high-mortality countries which have achieved the fourth millennium development goal with over two-thirds reduction in under-five mortality rate. However, the proportion of neonatal deaths continues to rise and recent studies reported low coverage of the essential interventions saving newborn lives. In the context of low uptake of health facility delivery, it is relevant to explore routine practices during home deliveries and, in this study, we explored the sequence of immediate newborn care practices and associated beliefs following home deliveries in rural communities in Ethiopia. Between April-May 2013, we conducted 26 semi-structured interviews and 2 focus group discussions with eligible mothers, as well as a key informant interview with a local expert in traditional newborn care practices in rural Basona woreda (district) near the urban town of Debrebirhan, 120 km from Addis Ababa, Ethiopia. The most frequently cited sequence of newborn care practices reported by mothers with home deliveries in the rural Basona woreda was to tie the cord, immediately bath then dry the newborn, practice ‘Lanka mansat’ (local traditional practice on newborns), give pre-lacteal feeding and then initiate breastfeeding. For ‘Lanka mansat’, the traditional birth attendant applies mild pressure inside the baby’s mouth on the soft palate using her index finger. This is performed believing that the baby will have ‘better voice’ and ‘speak clearly’ later in life. Coverage figures fail to tell the whole story as to why some essential interventions are not practiced and, in this study, we identified established norms or routines within the rural communities that determine the sequence of newborn care practices following home births. This might explain why some mothers delay initiation of breastfeeding and implementation of other recommended essential interventions saving newborn lives. An in-depth understanding of established routines is necessary, and community health extension workers require further training and negotiation skills in order to change the behaviour of mothers in practicing essential interventions while respecting local values and norms within the communities.