Track topics on Twitter Track topics that are important to you
Severe early onset epilepsies are often caused by de novo pathogenic variants. Few studies have reported the frequency of somatic mosaicism in parents of children with severe epileptic encephalopathies. Here we aim to investigate the frequency of mosaicism in the parents of children with epilepsy caused by alleged de novo variants. We tested parental genomic DNA derived from different tissues for 75 cases using targeted next-generation sequencing. Five parents (6.6%) showed mosaicism at minor allele frequencies of 0.8%-29% for the pathogenic variant detected in their offspring. Parental mosaicism was observed in the following genes: SCN1A, SCN2A, SCN8A, and STXBP1. One of the identified parents had epilepsy himself. Our results show that de novo events can occur already in parental tissue and in some cases can be detected in peripheral blood. Consequently, parents affected by low-grade mosaicism are faced with an increased recurrence risk for transmitting the pathogenic variant, compared to the overall recurrence risk for a second affected child estimated at approximately 1%. However, testing for parental somatic mosaicism will help identifying those parents who truly are at higher risk and will significantly improve genetic counseling in the respective families.
This article was published in the following journal.
The importance of gonadal mosaicism in families with apparently de novo mutations is being increasingly recognized. We report on two affected brothers initially suggestive of X-linked or autosomal rec...
Lynch syndrome (LS) is caused by germline mismatch repair (MMR) gene mutations. De novo MMR gene mutations are rare, and somatic mosaicism in LS is thought to be infrequent. We describe the first case...
Genetic epidemiology studies have shown that most epilepsies involve some genetic cause. In addition, twin studies have helped strengthen the hypothesis that in most patients with epilepsy, a complex ...
Over the past decade there has been a substantial increase in genetic studies of brain malformations, fueled by the availability of improved technologies to study surgical tissue to address the hypoth...
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with pathogenic / likely pathogenic (P/LP) variants in genes encoding the cardiac desmosomal proteins. Origin of these variants inc...
Mosaicism within an embryo is defined as the presence of two or more cell populations with different genotypes. Blastocysts classified as mosaic by Preimplamtation Genetic Testing for Aneu...
Genetic abnormalities in focal epilepsies are well known. A novel gene (DEPDC5) was identified, associated with various genotypes of epilepsies. Recently, DEPDC5 mutations were identified ...
Identify novel genetic variants causing skeletal dysplasia in Qatari populations and to additionally develop an understanding of how those variants influence skeletal biology at a molecula...
Data on transgenerational effects following nuclear accidents are important for understanding fully the consequences of parental exposure to ionizing radiation. Few studies to date have ha...
.Neurofibromatosis type 2 is an inherently autosomal dominant genetic disease, but cases of mosaicism or de novo mutation are not uncommon. the prevalence is estimated at 1 / 60,000. the c...
A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of ERECTILE DYSFUNCTION. It is also alleged to be an aphrodisiac.
An act of employing sorcery (the use of power gained from the assistance or control of spirits), especially with malevolent intent, and the exercise of supernatural powers and alleged intercourse with the devil or a familiar. (From Webster, 3d ed)
Naturally occurring genetic variations associated with drug response (e.g., dosage, extent and rate of metabolic processes). While these variants are not markers for GENETIC PREDISPOSITION TO DISEASE they influence PHARMACOKINETICS and pharmacodynamics and often occur on genes encoding drug metabolism enzymes and transporters (e.g., ANGIOTENSIN CONVERTING ENZYME; CYTOCHROME P-450 CYP2D6).
Congenital conditions of atypical sexual development associated with abnormal sex chromosome constitutions including MONOSOMY; TRISOMY; and MOSAICISM.
Reporting to parents or guardians about care to be provided to a minor (MINORS).
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...
Epilepsy is defined as a disorder of brain function characterized by recurrent seizures that have a sudden onset. (Oxford Medical Dictionary). A seizure is caused by a sudden burst of excess electrical activity in the brain, causing a tempora...