A diversity of retinal degenerations has been reported to be associated with biallelic variants in CRB1, the signature findings of CRB1 and the potential genotype-phenotype correlation have yet to be clarified. As preclinical research progresses, understanding the unique features of the CRB1 gene is crucial. Our multicenter retrospective cohort study summarizes comprehensive genotypic and phenotypic […]
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WDR45 variants as a major cause for a clinically variable intellectual disability syndrome from early infancy in females
Our genetic scan of WDR45 gene on 32 girls with intellectual disabilities (ID) found two having disease-causing WDR45 variants. Together with our previous findings from 19 girls subjected to whole genome sequencing, WDR45 variants accounts for 12% of female ID patients, apparently suggesting its major role in female ID patients. We also performed an extensive […]
Lynch syndrome diagnostic testing pathways in endometrial cancers: a nationwide English registry-based study
An estimated 3% of endometrial cancers are caused by Lynch Syndrome. These can be identified via a step-wise testing pathway of somatic tumour testing followed by germline gene testing. Using complete national data amalgamated from diagnostic laboratories via the English National Disease Registration Service, we conducted a retrospective national population-based observational study of Lynch Syndrome testing in […]
Commentary on Estimating cancer risk in carriers of Lynch syndrome variants in UK Biobank
Lynch syndrome is now considered to comprise four different heritable conditions, each caused by changes in a different gene and resulting in different levels of cancer risk. We previously calculated and published these risks according to age and sex, using the Prospective Lynch Syndrome Database. We also showed that colonoscopy does not prevent bowel cancer […]
UBTF haploinsufficiency associated with UBTF-related global developmental delay and distinctive facial features without neuroregression
The UBTF gene produces two important proteins, UBTF1 and UBTF2. A specific change in the UBTF gene, called a gain-of-function mutation, has been linked to a condition called CONDBA. However, until now, there haven’t been any reports of patients with a different kind of issue—having only one working copy of the UBTF gene (this is […]
Canadian College of Medical Geneticists: clinical practice advisory document – responsibility to recontact for reinterpretation of clinical genetic testing
There are currently differences and a lack of guidance for what to do about recontacting former patients when there may be changes in clinical genetics result interpretation. While there is no duty by law to do it, there may be a shared responsibility between the laboratory practitioners, ordering clinicians and the patient. This document discusses […]
Pathogenic SATB2 missense variants affecting p.Gly392 have variable functional implications and result in diverse clinical phenotypes
Our study describes eight individuals with SATB2-associated syndrome (SAS), an autosomal dominant disorder caused by variants in the SATB2 gene and characterized by developmental delay, behavioral challenges, craniofacial/dental problems, growth delay, and skeletal anomalies, all with variable severity. The individuals included carry genetic variants that affect the exact same location in the SATB2 protein but […]
Rare disease genomic testing in the UK and Ireland: promoting timely and equitable access
Equitable access to timely genomic testing for people affected by rare diseases is required to provide an accurate diagnosis early enough to inform key clinical decisions that modify outcome. This Position Statement describes best practice guidance for the specialist genomics workforce within the national health services in the UK and Ireland. It includes recommendations relating […]
Christianson syndrome across the lifespan: genetic mutations and longitudinal study in children, adolescents, and adults
Christianson syndrome (CS) is an X-linked brain disorder in males characterized by intellectual disability (ID), lack of language, postnatal microcephaly, ataxia, and epilepsy that is caused by mutations in Na+/H+ Exchanger 6 (NHE6). In the largest CS study to-date, we examined 44 CS probands, from 2 to 32 years old, with 31 unique NHE6 variants. […]
The PS4-Likelihood Ratio Calculator: Flexible allocation of evidence weighting for case-control data in variant classification
Observation of a genomic variant at higher frequency in cases with disease compared to population controls can be compelling evidence towards the variant being pathogenic. We present the PS4-Likelihood Ratio Calculator, a tool with which the user defines the odds ratio (representing anticipated underlying strength of disease association for a gene). A likelihood ratio towards […]