Multiple signals at the extended 8p23 locus are associated with susceptibility to systemic lupus erythematosus

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 […]

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15 years of research on Oral-Facial-Digital syndromes: from 1 to 16 causal genes

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 […]

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Novel and known ribosomal causes of Diamond-Blackfan anemia identified through comprehensive genomic characterization

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, […]

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A truncating mutation in CEP55 is the likely cause of MARCH, a novel syndrome affecting neuronal mitosis

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, […]

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Bi-allelic variants in COL3A1 encoding the ligand to GPR56 are associated with cobblestone-like cortical malformation, white matter changes and cerebellar cysts

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 […]

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A missense mutation in the CRBN gene that segregates with intellectual disability and self-mutilating behaviour in a consanguineous Saudi Family

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 […]

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GPRASP2, a Novel Causative Gene implicated in an X-Linked Recessive Syndromic Hearing Loss

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 […]

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No correlation between mtDNA amount and methylation levels at the CpG island of POLG exon 2 in wild-type and mutant human differentiated cells

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 […]

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Compound heterozygosity for severe and hypomorphic NDUFS2 mutations cause non-syndromic LHON-like optic neuropathy

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 […]

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