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, […]
Latest articles
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 […]
No correlation between mtDNA amount and methylation levels at the CpG island of POLG exon 2 in wild-type and mutant human differentiated cells (Contributed by Dr. Julie STEFFANN)
Mechanisms regulating mitochondrial DNA (mtDNA) amount according to developmental stage and tissue origin are still unknown. Recent works have suggested the role of epigenetic modification at a CpG island located in POLG gene, encoding the polymerase responsible for mtDNA synthesis. We found that this CpG island is highly methylated in human tissues, whatever developmental stages […]
Compound heterozygosity for severe and hypomorphic NDUFS2 mutations cause non-syndromic LHON-like optic neuropathy (Contributed by Dr. Jean-Michel ROZET)
Hereditary optic neuropathies (HON) are blinding conditions that affect the optic nerve which connects the eye to the brain. Mitochondrial (mt) and nuclear DNA mutations can cause HON. mtDNA mutations in complex I subunits of the respiratory chain cause a bilateral, painless, subacute disease known as Leber HON (LHON). Here, we report for the first […]
Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B (Contributed by Vijaya L Simhadri)
The genetic code is degenerate. Eighteen of the twenty core amino acids are each encoded by multiple, so-called synonymous codons. The Neutral Theory of Molecular Evolution suggests that synonymous codons will be unaffected by the selective evolutionary pressure and that synonymous mutations will be inconsequential to protein quality. However, recent reports refute this prediction. A […]
Precise long non-coding RNA modulation in visual maintenance and impairment (Contributed by Dr. Yehong Zhuo)
Long noncoding RNAs (lncRNAs), a class of DNA transcripts longer than 200 nucleotides with limited protein-coding potential, have been demonstradte to be crucial and pervasive cellular regulators in various physiological or pathological processes. Vision is a complex and vital perception that comprises 80% of the sensory information we receive. Based on current findings, our review […]