RESUMEN
Two variants in the ubiquitously expressed NHLRC2 gene have been reported to cause a lethal fibrotic cerebropulmonary disease termed fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome in three Finnish children. Our objective was to determine the genetic basis of disease in a new patient with clinical features of FINCA syndrome using whole-exome sequencing (WES) and confirmation by Sanger sequencing. The patient has one known and one novel variant in NHLRC2 (c.442T>G, p.D148Y and c.428C>A, p.H143P, respectively). p.H143P is extremely rare and is not present in the gnomAD database of >140,000 allele sequences from healthy humans. Both variants affect the highly conserved N-terminal thioredoxin (Trx)-like domain of NHLRC2 and are predicted to be damaging. We conclude that a compound heterozygous combination of a known and a novel variant in NHLRC2 causes FINCA syndrome in a 2-year-old Ukrainian patient, underscoring the importance of NHLRC2 as a central regulator of fibrosis.
Asunto(s)
Angiomatosis/genética , Neoplasias Encefálicas/genética , Cardiomegalia/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Enfermedades Pulmonares/genética , Enfermedades Neurodegenerativas/genética , Mutación Puntual , Secuencia de Aminoácidos , Cardiomegalia/patología , Preescolar , Fibrosis , Heterocigoto , Humanos , Masculino , Modelos Moleculares , Linaje , Conformación Proteica , Dominios Proteicos , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Síndrome , Secuenciación del ExomaRESUMEN
INTRODUCTION: Systemic hypertension (SH) is a major long-term health condition and is the leading cause of premature death among adults throughout the world, including developed, developing, and lesser developed countries.In recent years there has been a progressive increase in SH among children and adolescents. Epidemiological studies demonstrated an overall increase in the prevalence of hypertension. SH is rarely recorded isolated and is often combined with obesity or the metabolic syndrome. AIM OF THE STUDY: The aim of our research was to study the prevalence of overweight, obesity, and systemic hypertension in Ukrainian school children aged 10-16 years. MATERIAL AND METHODS: 540 pupils of two secondary schools in the city of Ternopil, aged 10-16 years, were involved. Blood pressure was measured under standard conditions using the standard technique. To assess the physical development of each child, indicators of body weight, height, waist circumferences and body mass index were compared with percentile tables. RESULTS: The study has demonstrated that the prevalence of overweight is 11.1% and obesity 4.8% among pupils of Ternopil. The elevated blood pressure was found in 50 % of overweight or obese pupils. SH was found in 13.3% of children (11.8% of girls and 15.1% of boys), where pre-hypertension (p<0,01) and SH 1st (p<0,01) stages were observed twice as often in boys than in girls, and normal BP was recorded less frequently (p<0,01). CONCLUSIONS: The boys are three times more often obese than girls and 1.4 times more often overweight. The blood pressure is directly correlated with increased BMI, waist and hip circumference in the examined children. The abdominal obesity is a predictor of hypertension in adolescents. The result of the present study has demonstrated the real epidemiology of obesity and systemic hypertension in children and adolescents, and should motivate family doctors and paediatricians to prevent this pathology in Ukraine.