Germline mutations of the APC gene, which encodes a multidomain protein of 2843 amino acid residues, cause familial adenomatous polyposis (FAP). Truncating mutations in APC extreme 3’-end are rare and have not been clearly associated with a specific phenotype. Here we studied 101 clinically characterized patients harboring truncating mutations in APC extreme 3’-end in order […]
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Complete loss of KCNA1 activity causes neonatal epileptic encephalopathy and dyskinesia
A patient presenting with a severe combination of dyskinesia and neonatal epileptic encephalopathy was sequenced by whole-exome sequencing, revealing a homozygous variant in KCNA1. This newly identified variant is the first to be reported to act in a recessive mode of inheritance in this gene. Functional analysis showed that mutant protein alone failed to produce functional channels, while […]
Increasing knowledge in IGF1R defects: lessons from 35 new patients
The IGF1R is a keystone of fetal growth regulation by mediating the effects of IGF-I and IGF-II. We detected 21 IGF1R defects in patients with fetal growth restriction, including 8 heterozygous CNVs and 10 heterozygous, 1 homozygous, and 1 compound-heterozygous SNVs. We validated a scoring system based on fetal and post-natal growth retardation, microcephaly and […]
Paediatric systemic lupus erythematosus as a manifestation of constitutional mismatch repair deficiency
Constitutional mismatch repair deficiency (CMMRD) is an autosomal recessive cancer predisposition syndrome, causing café au lait macules, brain malformations and and multiple tumors, mostly leukemia/ lymphoma, brain, and gastrointestinal cancer in the first two decades. Early recognition of CMMRD may allow tailored surveillance and genetic counseling, also for heterozygote carriers who have Lynch syndrome. We […]
Biallelic Mutations in CFAP65 Cause Male Infertility with Multiple Morphological Abnormalities of the Sperm Flagella in Humans and Mice
Male infertility due to multiple morphological abnormalities of the sperm flagella (MMAF) is a genetically heterogeneous disorder. Previous studies revealed several MMAF-associated genes, which account for approximately 60% of human MMAF cases. The pathogenic mechanisms of MMAF remain to be illuminated. In this study, we identified biallelic mutations of the CFAP65 gene in the MMAF […]
Homozygous damaging SOD2 variant causes lethal neonatal dilated cardiomyopathy
Cardiomyopathy, or a deterioration of the ability of the heart muscle to contract, generally leads to progressive heart failure. It is frequently inherited, and, because approximately 40% of affected children are likely to die within five years of diagnosis, being able to identify its genetic basis is particularly important. Now, we have identified a new […]
Presence of pathogenic copy number variants (CNVs) is correlated with socioeconomic status
Socio-economic status (SES) has profound effects on health outcomes. This paper shows that people with disease-causing small chromosomal variations (CNVs) tend to have lower SES. Interestingly, SES of individuals with milder inherited CNVs tends to be even lower than of individuals with more severe CNVs without any family history. These findings mean that future studies […]
Genetic aetiology of early infant deaths in a neonatal intensive care unit
This study investigated the genetic causes of early death in a 3-year death cohort from the NICU of Children’s Hospital of Fudan University. We identified 44 (19.7 %, 44/223) deceased newborns with genetic findings and 13 of them had medically actionable disorders based on genetic diagnosis. Multiple congenital malformation was the leading genetic cause of […]
Rapid, proteomic urine assay for monitoring progressive organ disease in Fabry disease
This works describes a new and non-invasive way to simultaneously monitor an inflammatory response, lysosomal dysfunction, kidney and cardiovascular disease. Fabry Disease is a condition where we cannot breakdown a glycolipid. This builds up in the body causing kidney and/or cardiovascular damage. Plasma lyso-Gb3 is the general lipid biomarker used to monitor response to treatment […]
Impact of DNA source on genetic variant detection from human whole-genome sequencing data
Whole-genome sequencing (WGS) is the most comprehensive genetic test possible, theoretically allowing the detection of all types of genetic variants. With decreasing DNA sequencing costs, we can now consider applying WGS to worldwide populations, but this requires the collection of DNA samples. While blood is the traditional source of DNA, saliva and buccal (cheek) samples […]