Remarkable advances in our understanding of epilepsies have occurred over the last 15 years. Concepts about etiology of epilepsies have been transformed from largely unknown to predominantly genetic through clinical genetic and molecular genetic advances. In this review we contrast the early breakthroughs in epilepsy genetics including the contribution of susceptibility alleles, de novo mutations […]
Latest articles
ARHGDIA: a novel gene implicated in nephrotic syndrome
Congenital nephrotic syndrome is a rare kidney disease in which affected infants lose protein in the urine and eventually develop kidney failure. Most cases are due to mutations in one of five genes. We have identified a mutation in a new gene, ARHGDIA, encoding Rho GDP dissociation inhibitor alpha (RhoGDIa) that is responsible for this […]
Exome sequencing identifies mutations in the gene TTC7A in French-Canadian cases with hereditary multiple intestinal atresia
Congenital multiple intestinal atresia is a fatal disorder affecting newborn infants, with the occurrence of numerous obstructions in the small and large intestines, sometimes associated with severe immune deficiency. A genetic origin for the disease was suspected but until now no specific gene had been identified. By performing genome-wide sequencing of DNA from five affected […]
TBC1D24 Truncating Mutation Resulting in Severe Neurodegeneration
Our patients had epilepsy onset in infancy as part of a severe disease affecting the brain that led to death in childhood. We found the underlying mutation. Previously two epilepsy families were described with defects in the same gene. The Italian patients had normal neurological and mental development whereas the Arab patients had moderate intellectual […]
Melanoma-prone families with CDK4 germline mutation: Phenotypic profile and associations with MC1R variants
Families with mutations in the genes CDKN2A or CDK4 have a very high risk of developing cutaneous malignant melanoma. CDKN2A melanoma families are well characterized, whereas a common description has been lacking for the much rarer CDK4 families. We have studied 17 CDK4 families from eight countries, the largest collection of such pedigrees to date. […]
Mutations in POLR3A and POLR3B are a major cause of hypomyelinating leukodystrophies with or without dental abnormalities and/or hypogonadotropic hypogonadism
Leukodystrophies are a group of hereditary neurodegenerative disorders characterized by abnormal white matter on brain imaging. Hypomyelinating leukodystrophies are a subtype of leukodystrophies caused by abnormal myelin deposition. Recently, our group reported that mutations in POLR3A and POLR3B genes were responsible for four hypomyelinating leukodystrophies with or without dental abnormalities and delayed puberty, and are […]
Whole Exome Sequencing Identifies a Mutation for a Novel Form of Corneal Intraepithelial Dyskeratosis
Corneal intraepithelial dyskeratosis is a rare condition, classically affecting American Haliwa-Saponi tribe members. Herein, we present a new form of this disease in a Caucasian French family, and the way we identified its causative gene. The proband presented with severe bilateral corneal involvement, associated with palmoplantar and laryngeal localizations. Analyses of the cornea and the […]
Mutations in TMEM231 cause Meckel–Gruber syndrome
Meckel Gruber syndrome is a multiple congenital malformation syndrome that represents the severe end of the ciliopathy phenotypic spectrum. It is caused by recessive mutations in a number of genes. In this study, we have identified two consanguineous families with Meckel Gruber syndrome and uncovered a novel recessive mutation in TMEM231 in each of them. […]
Role of PRRT2 in common paroxysmal neurological disorders: a gene with remarkable pleiotropy
Benign familial infantile epilepsy (BFIE) and paroxysmal kinesigenic dyskinesia (PKD) are two distinct neurological disorders that have been thought to have the same genetic basis, since the two disorders are sometimes seen together as Infantile Convulsions and Choreoathetosis (ICCA) syndrome and have each been mapped to the same region of the genome. The gene for […]
Deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation
Copy-number variations lead to extra or fewer copies of genetic material in the human genome. These changes are typically benign, but they may cause disease in some people. In this paper, we identify 35 individuals who have each lost genetic material in region 16q24.2 of chromosome 16. Many of these individuals have a cognitive disorder, […]