As babies develop, their skull needs to get bigger to give the developing brain enough space to grow. We study craniosynostosis, a serious condition (affecting ~1/2,000 children) that occurs when one or more gaps between the skull bones (cranial sutures) fuses too early. Here, we used high throughput DNA sequencing technologies in more than 1,600 […]
Latest articles
Calibration of polygenic risk scores is required prior to clinical implementation: results of three common cancers in UKB
Studies have shown a consistent trend between polygenic risk score percentiles and disease risk in populations, and this evidence is used to support its clinical use. However, in clinic, polygenic risk score values, not percentiles, are used for estimating disease lifetime risk. In this study, we assessed the calibration of polygenic risk score values for […]
Deep exploration of a CDKN1C mutation causing a mixture of Beckwith-Wiedemann and IMAGe syndromes revealed a novel transcript associated with developmental delay
We present a child with an unexpected combination of both Beckwith-Wiedemann syndrome (BWS), an imprinted overgrowth condition, and IMAGe syndrome, a growth-restricted condition. The child also has developmental delay and microcephaly, apparently unrelated features. However, all features can potentially be explained by a single CDKN1C delins mutation, de novo mosaic in the maternal grandfather, due […]
Phenotype and genotype spectra of a Chinese cohort with nephronophthisis-related ciliopathy
Nephronophthisis-related ciliopathies (NPH-RC) are important genetically disorders causing chronic renal failure (CRF) in children and adolescents.This group of diseases involved multiple pathogenic genes and organs.We firstly studied the genotype and phenotype spectra in a largest China cohort of NPHP-RC based on national register network (www.ccgkdd.com.cn). NPHP1 and NPHP3 are the most common pathogenic genes, and […]
Dysfunction of VIPR2 leads to myopia in humans and mice
Myopia incidence is reaching epidemic proportions in some communities, especially in East Asia regions. Meta-association analysis was used to determine if the vasoactive intestinal peptide receptor 2 (VIPR2) associated with myopia a human Chinese cohort, and then conform it using Vipr2-KO mice. Presence of variant in the VIPR2 gene and loss of VIPR2 function in […]
Linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with FOXG1 syndrome region
Over 2,400 years ago, Hippocrates noticed that eye misalignment, or strabismus, tended to cluster in families. This observation represents an early recognition of what we now recognize as genetic causes. However, genetic causes of isolated strabismus, which occur in the absence of other symptoms, remain elusive. In a large family, we identify a piece […]
Combining evidence for and against pathogenicity for variants in cancer susceptibility genes: CanVIG-UK consensus recommendations
Standardization of practice in classification of variants in cancer susceptibility genes has improved substantially since UK adoption of the 2015 American College of Medical Genetics (ACMG) framework. However, considerable inconsistency between laboratories persists, largely around how evidence items are weighted and combined. We present consensus recommendations from Cancer Variant Interpretation Group UK (CanVIG-UK), our national […]
MELAS-associated m.5541C>T mutation caused instability of mitochondrial tRNATrp and remarkable mitochondrial dysfunction
We found a pathogenic m.5541C>T mutation in the mitochondrial tRNATrp gene in a large MELAS family. This mutation firstly affected the maturation and stability of mitochondrial tRNATrp and impaired mitochondrial respiratory chain complex activities, followed by remarkable mitochondrial dysfunction. Surprisingly, we identified that the supplementation of taurine alone remarkably ameliorated the instability and the translation […]
Canadian College of Medical Geneticists (CCMG) points to consider: resuming genetic services in a pandemic—a summary
The COVID-19 pandemic has disrupted the provision of genetic care in Canada. As genetic services are asked to gradually resume, a roadmap is needed to ensure that clinical care decisions for at-risk patients are transparent and equitable, that postponed care is resumed and that patients with or waiting for a genetic diagnosis are not disproportionately […]
Inhibition of G-protein signaling in cardiac dysfunction of Intellectual Developmental Disorder with Cardiac Arrhythmia (IDDCA) syndrome
IDDCA (MIM #617173) is an ultra-rare autosomal recessive disorder caused by mutations in GNB5 gene. Genotype-phenotype correlation shows that homozygous or compound heterozygous missense variants are associated with an attenuated phenotype with mild intellectual disability (ID) and sinus node dysfunction, while homozygous null alleles cause severe ID with absent speech, epileptic encephalopathy, hypotonia and sinus […]