Mutations in the gene PLA2G6 cause neurodegeneration by a yet undefined mechanism. In this study we analyzed the Golgi and glycosylation in cultured skin fibroblasts in three patients with PLA2G6-associated neurodegeneration (PLAN). Although each patient had different mutations, all had altered Golgi morphology and protein O-linked glycosylation that were rescued by overexpression of wild type […]
Latest articles
The Regulatory Element READ1 Epistatically Influences Reading and Language, with both Deleterious and Protective Alleles
Dyslexia and Language Impairment (LI) are common learning disabilities that make written and spoken language difficult to process for affected individuals. Both disorders have a strong genetic component, but inheritance is complex and individual risk variants have been difficult to identify. In this study, we show that alleles of READ1, a genetic variant associated with […]
Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases
Familial Adenomatous Polyposis (FAP), caused by germline mutations in the tumor suppressor gene APC, is one of the most common types of hereditary colorectal cancer. However, in a considerable fraction of families the disease remains unexplained. This is the first study which comprehensively explored the impact of low-level APC mutational mosaicism. Multiple colorectal polyps in […]
Intellectual ability in tuberous sclerosis complex correlates with predicted effects of mutations on TSC1 and TSC2 proteins
Tuberous sclerosis complex (TSC) is a genetic disorder with a birth incidence of 1 in 6000, which is quite common for a ‘rare’ genetic disease. The two genes, their proteins and intracellular signalling pathways have been identified. TSC leads to multi-system involvement including benign tumours and very high rates of TSC-associated neuropsychiatric disorders. Some people […]
Homozygous missense mutation in the LMAN2L gene segregates with intellectual disability in a large consanguineous Pakistani family
We investigated a large consanguineous family from Pakistan comprising multiple affected individuals with intellectual disability and epilepsy. Using a combination of next-generation and classical sequencing methods, we identified a bi-allelic missense mutation p.R53Q in the LMAN2L gene only in the patients and not in the unaffected family members. LMAN2L encodes for a protein playing a […]
Congenital hyperinsulinism in children with paternal 11p uniparental isodisomy and Beckwith–Wiedemann syndrome
We report the largest group of patients to date with hyperinsulinism (HI) and Beckwith-Wiedemann syndrome (BWS). Our study shows that BWS children with severe, persistent HI have a particular form of BWS caused by two copies of part of chromosome 11 inherited from the father (paternal uniparental isodisomy for chromosome 11; pUPD11p). Three-fourths of these […]
UNC80 mutation causes a syndrome of hypotonia, severe intellectual disability, dyskinesia and dysmorphism, similar to that caused by mutations in its interacting cation channel NALCN
NALCN is a voltage-independent cation channel that controls neuronal excitability. NALCN is known to interact with two other proteins, UNC79 and UNC80, which together form an active channel complex in hippocampal neurons. Thus, regulation of the UNC79-UNC80-NALCN channel complex is extremely important for controlling neuronal excitability. Our study presents a novel syndrome of hypotonia, severe […]
Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin–Siris syndrome
The SOX11 gene encodes a transcription factor which regulates neuronal production during brain development. In mice, loss of SOX11 is associated with reduced brain size. In this study, Hempel et al identify deletions or de novo mutations of SOX11 in children with neurodevelopmental delay, microcephaly and dysmorphism. Some of the reported individuals had features of […]
Targeted massively parallel sequencing of a panel of putative breast cancer susceptibility genes in a large cohort of multiple-case breast and ovarian cancer families
The authors performed specific sequencing 17 known and putative breast cancer susceptibility genes in 660 women with familial breast cancer who did not carry a mutation the known susceptibility genes, BRCA1 or BRCA2. The authors then evaluated the putative cancer-related mutations and found in relevant family members to determine whether they were carried by affected […]
A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement
Dentists, geneticists and clinician-researchers studying tooth defects are often confronted by patients with genetic disorders that have striking dental defects such as the absence of some or several teeth, loss or defects in tooth enamel, and cleft palate among others. These defects can have a significant impact on the health and quality of life of […]