This study examined how the type of genetic mutation, function and health affect quality of life in Rett syndrome. Better walking and feeding skills and less frequent seizures were associated with better quality of life and poor sleep and behavioural difficulties with poorer quality of life. Compared to other mutations, individuals with the p.Arg294* mutation […]
Latest articles
Biallelic variants in BRCA1 gene cause a recognisable phenotype within chromosomal instability syndromes reframed as BRCA1 deficiency
BRCA1 gene is associated with breast-ovarian cancer susceptibility, however, carrying two variants in this gene causes a condition recognized as a very rare form of Fanconi Anemia. Here we present clinical features of nine individuals carrying two variants in BRCA1 gene, in order to understand the patients’ health risk. Features include growth failure, small head […]
Frameshift mutation of Timm8a1 gene in mouse leads to an abnormal mitochondrial structure in the brain, correlating with hearing and memory impairment
Deafness-Dystonia-Optic Neuronopathy (DDON) syndrome is a rare X-linked inherited disease characterized by progressive deafness, dystonia, ataxia, visual problems, and memory deficit, which is caused by mutations in the gene DDP1/TIMM8A. The encoded protein, Tim8a, is a mitochondrial protein. In the present study, we found a novel mutation in the DDP1 gene (NM_004085.3, c.82C>T, p.Q28X) and […]
Can population BRCA screening be applied in non-Ashkenazi Jewish populations? Experience in Macau population
BRCA mutation increases risk of breast and ovarian cancer. Identifying the mutation carriers is the first step to prevent the mutation-caused cancer. Population screening can reach comprehensive identification of the mutation carriers to prevent the cancer. However, this approach is considered only suitable for Ashkenazi Jewish population with high-frequent founder mutations, but not suitable for […]
Pathogenic variants in IMPG1 cause autosomal dominant and autosomal recessive retinitis pigmentosa
Vitelliform macular dystrophy (VMD) and retinitis pigmentosa (RP) are major causes of inherited visual impairment. Mutations in the IMPG1 gene have previously been described in patients with VMD. In the present study, we describe seven variants in IMPG1 in 11 families and provide two additional IMPG1-associated diagnoses: autosomal dominant and autosomal recessive RP. IMPG1 encodes […]
Biallelic mutations in the TOGARAM1 gene cause a novel primary ciliopathy
Cilia are essential subcellular structures present on most cell types. Their alterations is associated with distinct disorders affecting development, particularly brain anomalies. Many genes have been associated with primary ciliopathies, but some patients lack a molecular diagnosis. Molecular analysis in a family with a malformation disorder identified mutations in TOGARAM1, which is conserved in nematodes […]
Biallelic loss-of-function ZFYVE19 mutations are associated with congenital hepatic fibrosis, sclerosing cholangiopathy and high-GGT cholestasis
Mutations in ZFYVE19, which encodes a protein involved in division of cells and in regulation of the primary cilium (an incompletely understood structure in many but not all cells), that abolish ZFYVE19 protein expression underlie a form of bile-duct and liver disease for which children may require liver transplantation. This was not known before. Manifestations of ZFYVE19 disease […]
Congenital sensorineural hearing loss as the initial presentation of PTPN11-associated Noonan syndrome with multiple lentigines or Noonan syndrome: clinical features and underlying mechanisms
Germline variants in PTPN11 are the primary cause of Noonan syndrome with multiple lentigines (NSML) and Noonan syndrome (NS), which are both autosomal dominant congenital developmental disorders with high phenotypic variability that show substantial overlap in clinical features, such as facial dysmorphism, cardiovascular defects, hearing loss, and growth retardation. The NSML/NS phenotypes are extremely heterogeneous. […]
Data-driven modelling of mutational hotspots and in silico predictors in hypertrophic cardiomyopathy
In Mendelian disease genes, missense-variants may cluster in specific functional regions of the protein. Often, there is a complimentary depletion in controls due to population-level constraint. We developed two statistical methods to interrogate this signal, one for gene-association, another for variant interpretation. For gene-discovery efforts, we demonstrate how modeling clustering can improve power. For variant […]
Prenatal clinical manifestations in individuals with COL4A1/2 variants
Heterozygous pathogenic COL4A1/2 variants cause early-onset cerebrovascular diseases, including porencephaly and schizencephaly. Although most of them are developed during prenatal periods, little had been known about their prenatal clinical features. We identified 56 individuals with pathogenic COL4A1/2 variants, and obtained prenatal clinical information in 47 individuals. Only about 30% of them exhibited prenatal findings that […]