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 […]
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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, […]
High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome
PTEN hamartoma tumor syndrome (PHTS) encompasses several clinical syndromes with germline mutations in the PTEN tumor suppressor gene, including Cowden syndrome, characterized by an increased risk of breast and thyroid cancers. Because PHTS is rare, data regarding cancer risks are limited. We recruited a significant number of PHTS patients with germline PTEN mutations from the […]
Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome
Auriculocondylar syndrome (ACS) is characterised by an ear malformation known as a “question mark ear” and variable under-development of the lower jaw. Recently, mutations in two genes, PLCB4 and GNAI3,were identified as the cause of ACS. We identified further mutations in these genes in a series of ACS patients, but not in patients with related […]
Mutations of NANOS1, a human homologue of the Drosophila morphogen, are associated with a lack of germ cells in testes or severe oligo-astheno-teratozoospermia
The genetic causes of infertility are not well understood, while they seem quite frequent. We found that mutations of a gene, NANOS1, are possibly among the causes of human male reproduction failure, as they are in the fruit fly. Depending on location within the gene, these mutations can cause a complete lack of germ cells […]
Breakpoint mapping by Next Generation Sequencing reveals causative gene disruption in patients carrying apparently balanced chromosome rearrangements with intellectual deficiency and/or congenital malformations
Apparently balanced chromosomal rearrangements (ABCR) are associated with an abnormal phenotype in 6 % of cases. This may be due to the disruption of genes at the breakpoint. However, conventional methods of breakpoint cloning are laborious and time-consuming. Here, we used whole-genome next-generation sequencing (NGS) to rapidly locate breakpoints at the molecular level in four […]
Mutation of HERC2 causes developmental delay with Angelman-like features
Angelman syndrome is a rare genetic condition characterised by severe learning difficulties and neurological problems. The majority of cases result from a deletion of part of chromosome 15 which usually affects a gene called E6AP, thought to be the primary molecule responsible Angelman syndrome. HERC2 is another gene that is commonly deleted in Angelman syndrome […]