Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

Aarskog-Scott syndrome: a clinical study based on a large series of 111 male patients with a pathogenic variant in and management recommendations.

Background: Aarskog-Scott syndrome (AAS) is a rare condition with multiple congenital anomalies, caused by hemizygote variants in the gene. Its description was based mostly on old case reports, in whom a molecular diagnosis was not always available, or on small series. The aim of this study was to better delineate the phenotype and the natural history of AAS and to provide clues for the diagnosis and the management of the patients.

Loss of DOT1L function disrupts neuronal transcription, animal behavior, and leads to a novel neurodevelopmental disorder.

Individuals with monoallelic pathogenic variants in the histone lysine methyltransferase DOT1L display global developmental delay and varying congenital anomalies. However, the impact of monoallelic loss of remains unclear. Here, we present a largely female cohort of 11 individuals with variants with developmental delays and dysmorphic facial features.

Variants in LRRC7 lead to intellectual disability, autism, aggression and abnormal eating behaviors.

Members of the leucine rich repeat (LRR) and PDZ domain (LAP) protein family are essential for animal development and histogenesis. Densin-180, encoded by LRRC7, is the only LAP protein selectively expressed in neurons. Densin-180 is a postsynaptic scaffold at glutamatergic synapses, linking cytoskeletal elements with signalling proteins such as the α-subunit of Ca/calmodulin-dependent protein kinase II.