Early onset epilepsy with resistance to common anticonvulsants can be due to genetic defects that respond to high doses of vitamin B6. We describe four patients with neonatal, pyridoxine (vitamin B6) responsive seizures and disease causing variants in the PROSC gene, which regulates vitamin B6 metabolism in body cells. Three patients had favorable outcome with […]
Latest articles
Somatic mosaicism containing double mutations in PTCH1 revealed by generation of induced pluripotent stem cells from nevoid basal cell carcinoma syndrome (Contributed by Prof. Toshiyuki Miyashita)
As next generation sequencers are widely used, somatic mosaicism is thought to be more common than previously expected. We report a mosaic patient with nevoid basal cell carcinoma syndrome, a genetic condition featured by minor anomalies and high prevalence of cancers such as basal cell carcinoma and medulloblastoma. The patient had a germline PTCH1 mutation, […]
Multiple signals at the extended 8p23 locus are associated with susceptibility to systemic lupus erythematosus (Contributed by Dr. F. Yesim Demirci)
One of the major susceptibility loci identified for Systemic lupus erythematosus (SLE) lies within a common large inversion polymorphism region on chromosome 8p23. In this study, we further investigated the ‘extended’ 8p23 locus (~4 Mb) where we observed multiple SLE signals and assessed these signals for their relation to the inversion affecting this region. The […]
15 years of research on Oral-Facial-Digital syndromes: from 1 to 16 causal genes (Contributed by Dr. Ange-Line Bruel)
Oral-facial-digital syndromes (OFDS) are rare genetic disorders characterized by the association of abnormalities of the face, oral cavity and extremities. Molecular bases were poorly known but we suspected the involvement of ciliary genes. Using whole-exome sequencing in 24 OFDS cases, we identified causal variants in five new genes, two genes previously implicated in OFDS and […]
Novel and known ribosomal causes of Diamond-Blackfan anemia identified through comprehensive genomic characterization (Contributed by Dr. Payal P. Khincha)
Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome primarily caused by defects in ribosome biology. It is associated with physical anomalies and high risk of specific cancers. We performed comprehensive genomic analyses of 35 genetically uncharacterized DBA families participating in the National Cancer’s Institute’s DBA cohort (ClinicalTrials.gov Identifier: NCT00027274). Using whole exome sequencing, […]
A truncating mutation in CEP55 is the likely cause of MARCH, a novel syndrome affecting neuronal mitosis (Contributed by Dr. Patrick Frosk)
Hydranencephaly, a congenital anomaly caused by destruction of the cerebral hemispheres is usually found in isolation. We report a family in which three fetuses displayed multinucleated neurons, anhydramnios, renal dysplasia, and cerebellar hypoplasia together with hydranencephaly, a novel syndrome we have named MARCH. Sequencing revealed the cause to be a homozygous truncating mutation in CEP55, […]
Bi-allelic variants in COL3A1 encoding the ligand to GPR56 are associated with cobblestone-like cortical malformation, white matter changes and cerebellar cysts (Contributed by Prof. Anna Jansen)
Collagens are important constituents of connective tissue but are also present in the membrane lining the surface of the brain. The COL3A1 gene encodes the chains of type III procollagen. Mutation of one copy of this gene results in vascular Ehlers Danlos syndrome (EDS), a connective tissue disorder. We now have discovered that mutations of […]
A missense mutation in the CRBN gene that segregates with intellectual disability and self-mutilating behaviour in a consanguineous Saudi Family (Contributed by Atia Sheereen)
Here, we report five members affected with severe intellectual disability, developmental delays, seizures, and self-mutilation in a large consanguineous family from Saudi Arabia. Clinical whole-exome sequencing in the proband revealed a pathogenic variant in the CRBN gene, which segregated in the family. CRBN protein is known to play a role in memory and learning by […]
GPRASP2, a Novel Causative Gene implicated in an X-Linked Recessive Syndromic Hearing Loss (Contributed by Professor Xin Cao)
We reported a novel X-linked recessive syndromic hearing loss (SHL) combined with unique and unrecognized clinical features in a five-generation Chinese family. To identify the genetic cause of X-linked SHL, targeted X-chromosome exome sequencing (XES) was conducted. A 2-base pair missense mutation (c.1717_1718GC>AA, p.A573N) in the G protein-coupled receptor associated sorting protein 2 (GPRASP2) gene […]
A liminal stage after predictive testing for Huntington disease (Contributed by Dr. Alexandra Durr)
Does knowledge of being a carrier of the pathological Huntington disease mutation trigger onset of the disease, influence self-awareness and allow carriers to identify symptoms of disease onset? These are questions raised by persons who requested presymptomatic testing and we went back to 75 of them. We showed that having motor signs on examination did […]