Mitral annular disjunction (MAD) is supposed to be the anatomic substrate of mitral valve prolapse (MVP) and ventricular arrhythmias, whereas little is known about its molecular genesis, if any. Herein, we conducted the initial genetic screening among sporadic and familial MAD cases. Our findings supported that longitudinally extensive MAD, rather than MAD with any distance, […]
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Evaluation of the clinical, biochemical, genotype and prognosis of mut-type methylmalonic acidemia in 365 Chinese cases
Methylmalonic academia is the most common inherited organic acid metabolic disease in China, which is usually considered to have a poor prognosis. We recruited a large cohort of 365 mut-type MMA patients, investigated their phenotype and genotype. Participation in tandem mass spectrometry expanded newborn screening, vitamin B12 responsive and late onset are favorable factors for […]
Congenital mirror movements are associated with defective polymerisation of RAD51
To date, only few mutations in the RAD51 gene were associated to Congenital Mirror Movements (CMM), a rare genetic disorder for which affected patients cannot perform unimanual or asymmetric bimanual movements. In our study, identification of new mutations in RAD51 allowed to confirm haploinsufficiency of RAD51 in CMM and to demonstrate that compensation at the […]
Ureteropelvic junction obstruction with primary lymphoedema associated with CELSR1 variants
Many genes have been linked to primary lymphedema, yet they currently explain only about 30% of the patients. Moreover, there is no cure for the disease yet. A better understanding of the underlying causes should enable the development of novel therapeutic approaches. In this study, we have detailed the clinical phenotype of patients with CELSR1 […]
Genetic features and kidney morphological changes in women with X-linked Alport syndrome
X-linked Alport syndrome (XLAS) is an hereditary kidney disease caused by the pathogenic variants in COL4A5 gene and usually has heterogeneous phenotypes, especially in females. Here, we collected the genetic, clinical, and pathological data from a cohort of XLAS and conducted a comparative analysis of female and male patients. We found a higher incidence of […]
A model for the return and referral of all clinically significant secondary findings of genomic sequencing
Genomic sequencing (GS) has the capability of identifying a broad range of clinically significant secondary findings (SFs) beyond medically actionable findings. Healthcare resources and capacity constraints of returning and managing all clinically significant SFs represent major barriers to implementation of GS. We present a model for the return and referral of all clinically significant SFs […]
Craniofacial features of POLR3-related leukodystrophy caused by biallelic variants in POLR3A, POLR3B and POLR1C
RNA polymerase III-related or 4H (POLR3-HLD) is a genetic disorder that affects the white matter of the brain. It is caused by disease-causing variants in POLR3A, POLR3B, POLR1C or POLR3K. To this date, description of craniofacial features in individuals with POLR3-HLD is limited. Here, we explore and assess the craniofacial features of 31 patients with […]
Pulmonary function and structure abnormalities in children and young adults with osteogenesis imperfecta point to intrinsic and extrinsic lung abnormalities
Lung disease is the major cause of illness and death in individuals with osteogenesis imperfecta (OI), a collagen-related bone disorder. Previously, scoliosis and chest wall deformities were considered responsible for abnormal lung function in OI. We studied children and adults with several types of OI using lung function tests, X-Rays and lung CTs. Most patients […]
The phenotypic differences of C9ORF72 gene positive and negative amyotrophic lateral sclerosis: A comparative case series
Amyotropic lateral sclerosis (ALS) is the commonest form of motor neuron disease, with some cases caused by mutations in the C9ORF72 gene. At our tertiary neurosciences clinic, we compared a group of ALS patients with the C9ORF72 mutation to a group without the mutation. Patients with the C9ORF72 mutation were more likely to present with […]
Variants in the gene DNA2 causes Rothmund-Thomson syndrome-like presentation
Rothmund-Thomson syndrome is a rare genetic disorder caused by variants in both copies of ANAPC1 or RECQL4 genes. We report on six Brazilian individuals and two siblings of Swiss/Portuguese ancestry who presented severe short stature, poikiloderma and congenital ocular anomalies. Genomic analysis revealed that all patients harbored variants in both copies of DNA2, one variant, […]