7 research outputs found
The phenotypic and molecular genetic spectrum of Alstrom syndrome in 44 Turkish kindreds and a literature review of Alstrom syndrome in Turkey
Alstrom syndrome (ALMS) is an autosomal recessive disease characterized by multiple organ involvement, including neurosensory vision and hearing loss, childhood obesity, diabetes mellitus, cardiomyopathy, hypogonadism, and pulmonary, hepatic, renal failure and systemic fibrosis. Alstrom Syndrome is caused by mutations in ALMS1, and ALMS1 protein is thought to have a role in microtubule organization, intraflagellar transport, endosome recycling and cell cycle regulation. Here, we report extensive phenotypic and genetic analysis of a large cohort of Turkish patients with ALMS. We evaluated 61 Turkish patients, including 11 previously reported, for both clinical spectrum and mutations in ALMS1. To reveal the molecular diagnosis of the patients, different approaches were used in combination, a cohort of patients were screened by the gene array to detect the common mutations in ALMS1 gene, then in patients having any of the common ALMS1 mutations were subjected to direct DNA sequencing or next-generation sequencing for the screening of mutations in all coding regions of the gene. In total, 20 distinct disease-causing nucleotide changes in ALMS1 have been identified, eight of which are novel, thereby increasing the reported ALMS1 mutations by 6% (8/120). Five disease-causing variants were identified in more than one kindred, but most of the alleles were unique to each single patient and identified only once (16/20). So far, 16 mutations identified were specific to the Turkish population, and four have also been reported in other ethnicities. In addition, 49 variants of uncertain pathogenicity were noted, and four of these were very rare and probably or likely deleterious according to in silico mutation prediction analyses. ALMS has a relatively high incidence in Turkey and the present study shows that the ALMS1 mutations are largely heterogeneous; thus, these data from a particular population may provide a unique source for the identification of additional mutations underlying Alstrom Syndrome and contribute to genotype-phenotype correlation studies
Pregnancy and neonatal outcomes of COVID -19: coreporting of common outcomes from PAN-COVID and AAP-SONPM registries
Objective
Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARSâCoVâ2) infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and Global Pregnancy and Neonatal outcomes in COVIDâ19 (PANâCOVID) study and the American Academy of Pediatrics (AAP) Section on NeonatalâPerinatal Medicine (SONPM) National Perinatal COVIDâ19 Registry.
Methods
This was an analysis of data from the PANâCOVID registry (1 January to 25 July 2020), which includes pregnancies with suspected or confirmed maternal SARSâCoVâ2 infection at any stage in pregnancy, and the AAPâSONPM National Perinatal COVIDâ19 registry (4 April to 8 August 2020), which includes pregnancies with positive maternal testing for SARSâCoVâ2 from 14âdays before delivery to 3âdays after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PANâCOVID results are presented overall for pregnancies with suspected or confirmed SARSâCoVâ2 infection and separately in those with confirmed infection.
Results
We report on 4005 pregnant women with suspected or confirmed SARSâCoVâ2 infection (1606 from PANâCOVID and 2399 from AAPâSONPM). For obstetric outcomes, in PANâCOVID overall and in those with confirmed infection in PANâCOVID and AAPâSONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was preterm (<â37âweeks' gestation) in 12.0% of all women in PANâCOVID, in 16.1% of those women with confirmed infection in PANâCOVID and in 15.7% of women in AAPâSONPM. Extreme preterm delivery (<â27âweeks' gestation) occurred in 0.5% of cases in PANâCOVID and 0.3% in AAPâSONPM. Neonatal SARSâCoVâ2 infection was reported in 0.9% of all deliveries in PANâCOVID overall, in 2.0% in those with confirmed infection in PANâCOVID and in 1.8% in AAPâSONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a smallâforâgestationalâage (SGA) neonate were 8.2% in PANâCOVID overall, 9.7% in those with confirmed infection and 9.6% in AAPâSONPM. Mean gestationalâageâadjusted birthâweight Zâscores were â0.03 in PANâCOVID and â0.18 in AAPâSONPM.
Conclusions
The findings from the UK and USA registries of pregnancies with SARSâCoVâ2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a SGA infant or early neonatal death were comparable to those in historical and contemporaneous UK and USA data. Although maternal death was uncommon, the rate was higher than expected based on UK and USA population data, which is likely explained by underascertainment of women affected by milder or asymptomatic infection in pregnancy in the PANâCOVID study, although not in the AAPâSONPM study. The data presented support strong guidance for enhanced precautions to prevent SARSâCoVâ2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of pregnant women and women planning pregnancy. Copyright © 2021 ISUOG. Published by John Wiley & Sons Ltd