Impaired development and function of GnRH neurons leads to isolated hypogonadotropic hypogonadism (IHH), characterized by delayed/absent puberty and/or infertility. IHH frequently associated with additional phenotypes, such as sensorineural deafness, coloboma, synkinesis, craniofacial abnormalities, and renal agenesis. In this report, we found DUSP6, an inhibitor of FGFR1, mutated in IHH in an autosomal dominant manner. IHH […]
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Diagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS) (Contributed by Dr. Nan Wu)
Early-onset scoliosis (EOS), defined as clinical presentation of scoliosis before 10 years of age, can be associated with progressive pulmonary compromise and severe dysmorphic gross skeletal appearance if left untreated. In this study, Zhao et al. performed exome sequencing on a Chinese cohort of 447 patients with operative EOS and an US cohort of 13 […]
15q11.2 deletion is enriched in patients with total anomalous pulmonary venous connection (Contributed by Dr. Bo Wang)
15q11.2 has been associated a wide range of developmental such as neuropsychical diorders. In the study, we discovered that total anomalous pulmonary venous connection (TAPVC), A rare form of CHD, is significantly associated with 15q11.2 deletion. Using induced pluripotent stem (iPS) cells coupled with in vitro cardiomyocyte differentiation experiments, we showed that the iPS cells […]
Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients (Contributed by Dr. Bekim Sadikovic)
Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuromuscular disorder affecting more than 1 in 2500 people. Molecular defects that cause CMT are complex and involve large number of genes. This is the first Canadian study describing results of clinical genetic testing of nearly 3000 patients. This is also the largest patient cohort published to […]
Understanding polygenic models, their development and the potential application of polygenic scores in healthcare (Contributed by Dr. Chantal Babb de Villiers)
The use of genomic information in the form of polygenic scores as a predictive biomarker for common diseases has been an area of increasing interest. Methods applied in this field have evolved rapidly recently, with several methods proposed in generating these scores. An understanding of these methodological aspects is useful for considerations around implementation in […]
Uptake of pre-symptomatic testing for BRCA1 and BRCA2 is age, gender, offspring and time dependent (Contributed by Dr. Claire Forde)
Predictive BRCA1/2 testing, offered to healthy individuals after a BRCA1/2 gene change is identified in an affected family member, allows relatives to undergo cancer risk assessment and consider early cancer detection and risk-reduction strategies. This study is the largest assessment of BRCA1/2 predictive testing uptake in close relatives, encompassing 5669 individuals from 1564 families, for […]
Novel genetic characterisation and phenotype correlation in von Hippel-Lindau (VHL) disease based on the Elongin C binding site: a large retrospective study (Contributed by Dr. Haibiao Xie)
The highlight of this study is that, based on the current largest VHL patient database and blood sample bank in China, the impact of different gene mutation types of VHL disease on tumor risk and prognosis was analyzed for the first time from the perspective of the Elongin C binding site mutation (EM). This study […]
Identifying novel oncogenic RET mutations and characterising their sensitivity to RET-specific inhibitors (Contributed by Dr. Yu Yao)
Mutations in a cancer-related gene called RET were mainly found in certain cancers such as thyroid cancer. By analyzing large-scale DNA sequencing data from 37,056 cancer patients, we discovered RET mutations in multiple other cancers, mostly at low frequencies. In addition, we identified several novel RET mutations that can drive tumor formation, and some newly […]
Identification of known and unknown genes associated with mitral valve prolapse using an exome slice methodology (Contributed by Dr. Aniek van Wijngaarden)
This study presents the first, large-scale exome-based analysis in patients with (familial) mitral valve prolapse (MVP). We confirmed the occurrence of variant(s) in previously reported genes and proposed possible novel candidate genes for MVP, mostly cardiomyopathy genes. Our findings support familial screening in MVP patients in order to eventually identify affected relatives at an early […]
Medical and neurobehavioural phenotypes in carriers of X-linked ichthyosis-associated genetic deletions in the UK Biobank (Contributed by Dr. William Davies)
X-linked ichthyosis (XLI) is a skin disorder caused by a genetic deletion carried by approximately 7 million individuals worldwide. Brcic and colleagues use the power of the UK Biobank (comprising ~0.5 million individuals recruited from the UK general population) to show that carriers of XLI-associated deletions are at increased risk of mood symptoms and mild […]