Dataset Information

Recessive loss of function PIGN alleles, including an intragenic deletion with founder effect in La Reunion Island, in patients with Fryns syndrome.

ABSTRACT: Fryns syndrome (FS) is a multiple malformations syndrome with major features of congenital diaphragmatic hernia, pulmonary hypoplasia, craniofacial dysmorphic features, distal digit hypoplasia, and a range of other lower frequency malformations. FS is typically lethal in the fetal or neonatal period. Inheritance is presumed autosomal recessive. Although no major genetic cause has been identified for FS, biallelic truncating variants in PIGN, encoding a component of the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway, have been identified in a limited number of cases with a phenotype compatible with FS. Biallelic variants in PIGN, typically missense or compound missense with truncating, also cause multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1). Here we report six further patients with FS with or without congenital diaphragmatic hernia and recessive loss of function PIGN alleles, including an intragenic deletion with a likely founder effect in La Réunion and other Indian Ocean islands. Our results support the hypothesis that a spectrum of phenotypic severity is associated with recessive PIGN variants, ranging from FS at the extreme end, caused by complete loss of function, to MCAHS1, in which some residual PIGN function may remain. Our data add FS resulting from PIGN variants to the catalog of inherited GPI deficiencies caused by the disruption of the GPI-anchor biosynthesis pathway.

SUBMITTER: Alessandri JL

PROVIDER: S-EPMC5839001 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Recessive loss of function PIGN alleles, including an intragenic deletion with founder effect in La Réunion Island, in patients with Fryns syndrome.

Alessandri Jean-Luc JL Gordon Christopher T CT Jacquemont Marie-Line ML Gruchy Nicolas N Ajeawung Norbert F NF Benoist Guillaume G Oufadem Myriam M Chebil Asma A Duffourd Yannis Y Dumont Coralie C Gérard Marion M Kuentz Paul P Jouan Thibaud T Filippini Francesca F Nguyen Thi Tuyet Mai TTM Alibeu Olivier O Bole-Feysot Christine C Nitschké Patrick P Omarjee Asma A Ramful Duksha D Randrianaivo Hanitra H Doray Bérénice B Faivre Laurence L Amiel Jeanne J Campeau Philippe M PM Thevenon Julien J

European journal of human genetics : EJHG 20180112 3

Fryns syndrome (FS) is a multiple malformations syndrome with major features of congenital diaphragmatic hernia, pulmonary hypoplasia, craniofacial dysmorphic features, distal digit hypoplasia, and a range of other lower frequency malformations. FS is typically lethal in the fetal or neonatal period. Inheritance is presumed autosomal recessive. Although no major genetic cause has been identified for FS, biallelic truncating variants in PIGN, encoding a component of the glycosylphosphatidylinosit ...[more]

PMID: 29330547

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Project description:BackgroundFor decades La Réunion has experienced a number of epidemics that have resulted in efforts to control the density of Aedes species on this Island. This study was conducted to assess household-level expenditure on protective measures against mosquito nuisance on the Island of La Réunion in 2012.Methodology/principal findingsData was collected during a cross-sectional survey of 1024 households and used to determine the relationship between the use of chemically-based protective measures and subjective and objective indicators of the density of Aedes albopictus. The average household expenditure in July 2012 was USD 9.86 and the total household-level expenditure over a one-year period was extrapolated to USD 28.05million (range: USD 25.58 million to USD 30.76 million). Much of this money was spent on measures thought to be relatively ineffective against Aedes mosquitoes. Expenditure on protective measures was not influenced by the level of knowledge on mosquitoes or by the visual nuisance they generated at home, but rather by the perception of risk related to a future epidemic of chikungunya and socioeconomic factors. Most importantly, household spending on protective measures was found to be influenced by a measure of zone-level mosquito density (the Breteau index), but not by objective indicators of the presence of mosquitoes within or around the house.Conclusions/significanceHousehold-level expenditure on chemically-based protective measures is high when compared to the investment made by public entities to achieve vector control, and it is differentially influenced by subjective and objective measures of mosquito density. The current situation could be improved, firstly by ensuring that the public is well-informed about mosquitoes and the effectiveness of various protective measures, and secondly by implementing interventions that could either complement current vector-control strategies and improve their effectiveness on a country-level, or that would steer the population toward the appropriate behaviours.

Project description:BackgroundAn outbreak of chikungunya virus affected over one-third of the population of La Réunion Island between March 2005 and December 2006. In June 2005, we identified the first case of mother-to-child chikungunya virus transmission at the Groupe Hospitalier Sud-Réunion level-3 maternity department. The goal of this prospective study was to characterize the epidemiological, clinical, biological, and radiological features and outcomes of all the cases of vertically transmitted chikungunya infections recorded at our institution during this outbreak.Methods and findingsOver 22 mo, 7,504 women delivered 7,629 viable neonates; 678 (9.0%) of these parturient women were infected (positive RT-PCR or IgM serology) during antepartum, and 61 (0.8%) in pre- or intrapartum. With the exception of three early fetal deaths, vertical transmission was exclusively observed in near-term deliveries (median duration of gestation: 38 wk, range 35-40 wk) in the context of intrapartum viremia (19 cases of vertical transmission out of 39 women with intrapartum viremia, prevalence rate 0.25%, vertical transmission rate 48.7%). Cesarean section had no protective effect on transmission. All infected neonates were asymptomatic at birth, and median onset of neonatal disease was 4 d (range 3-7 d). Pain, prostration, and fever were present in 100% of cases and thrombocytopenia in 89%. Severe illness was observed in ten cases (52.6%) and mainly consisted of encephalopathy (n = 9; 90%). These nine children had pathologic MRI findings (brain swelling, n = 9; cerebral hemorrhages, n = 2), and four evolved towards persistent disabilities.ConclusionsMother-to-child chikungunya virus transmission is frequent in the context of intrapartum maternal viremia, and often leads to severe neonatal infection. Chikungunya represents a substantial risk for neonates born to viremic parturients that should be taken into account by clinicians and public health authorities in the event of a chikungunya outbreak.

Dataset Information

Recessive loss of function PIGN alleles, including an intragenic deletion with founder effect in La Reunion Island, in patients with Fryns syndrome.

Publications

Recessive loss of function PIGN alleles, including an intragenic deletion with founder effect in La Réunion Island, in patients with Fryns syndrome.

Similar Datasets

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