Browsing by Author "Rutka, Katrina"

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    Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus
    (2017-12-01) Cipriani, Valentina; Silva, Raquel S.; Arno, Gavin; Pontikos, Nikolas; Kalhoro, Ambreen; Valeina, Sandra; Inashkina, Inna; Audere, Mareta; Rutka, Katrina; Puech, Bernard; Michaelides, Michel; Van Heyningen, Veronica; Lace, Baiba; Webster, Andrew R.; Moore, Anthony T.; Rīga Stradiņš University
    Autosomal dominant North Carolina macular dystrophy (NCMD) is believed to represent a failure of macular development. The disorder has been linked to two loci, MCDR1 (chromosome 6q16) and MCDR3 (chromosome 5p15-p13). Recently, non-coding variants upstream of PRDM13 (MCDR1) and a duplication including IRX1 (MCDR3) have been identified. However, the underlying disease-causing mechanism remains uncertain. Through a combination of sequencing studies on eighteen NCMD families, we report two novel overlapping duplications at the MCDR3 locus, in a gene desert downstream of IRX1 and upstream of ADAMTS16. One duplication of 43 kb was identified in nine families (with evidence for a shared ancestral haplotype), and another one of 45 kb was found in a single family. Three families carry the previously reported V2 variant (MCDR1), while five remain unsolved. The MCDR3 locus is thus refined to a shared region of 39 kb that contains DNAse hypersensitive sites active at a restricted time window during retinal development. Publicly available data confirmed expression of IRX1 and ADAMTS16 in human fetal retina, with IRX1 preferentially expressed in fetal macula. These findings represent a major advance in our understanding of the molecular genetics of NCMD and provide insights into the genetic pathways involved in human macular development.
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    Incidence and outcomes of patients with functionally univentricular heart born in Latvia, 2007 to 2015
    (2018-07) Rutka, Katrina; Lubaua, Inguna; Ligere, Elina; Smildzere, Amanda; Ozolins, Valts; Balmaks, Reinis; Department of Anaesthesiology, Intensive Care and Clinical simulations; Department of Paediatrics; Department of Clinical Skills and Medical Technologies
    Background and Objectives: A functionally univentricular heart is the term used to describe congenital heart defects where it is impossible to restore two pumping chambers. These lesions are associated with high mortality, morbidity, and medical resource utilization. The aim of this study was to review incidence and outcomes of patients with a functionally univentricular heart at the only pediatric cardiac surgery center in Latvia. Methods: We performed a retrospective review of medical records of (i) all children with a functionally univentricular heart treated at the Clinic of Pediatric Cardiology and Cardiac Surgery, and (ii) all prenatally diagnosed cases of univentricular heart at Children’s Clinical University Hospital in Latvia. We reviewed data regarding children born from January 1, 2007, to December 31, 2015. The children’s cardiac anatomy and interventions were categorized in accordance with the International Pediatric and Congenital Cardiac Code (v3.3). Results: During the study period, 49 patients with a functionally univentricular heart were admitted to Children’s Clinical University Hospital with a corrected incidence of 0.69 per 1000 live births per year. There were 26 patients that had a hypoplastic left ventricle, and 22 patients that had a hypoplastic right ventricle, while one patient had an indeterminate ventricle. Thirty (61.2%) patients had died by the end of data collection. Twenty-one of the 30 deaths occurred before or immediately after stage I surgical palliation. Cumulative neonatal and 5-year survival of patients with a hypoplastic right ventricle was 81.8% and 63.6%, respectively; for patients with hypoplastic left ventricle—46.2% and 17.3%, respectively. Discussion: This is the first mid-term outcome study of patients with a univentricular heart in Latvia. The high mortality reflects the challenges of a small-volume, developing congenital cardiac surgery center. Data from this study will be used as a baseline for quality improvement.