• Combining evidence for and against pathogenicity for variants in cancer susceptibility genes: CanVIG-UK consensus recommendations 

  Ellard, Sian (HighWire, 2021-05)

  Accurate classification of variants in cancer susceptibility genes (CSGs) is key for correct estimation of cancer risk and management of patients. Consistency in the weighting assigned to individual elements of evidence ...

• KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation 

  Rankin, Julia; Baple, Emma L. (Oxford University Press, 2020-12-05)

  Heterozygous mutations in KMT2B are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving ...

• No association between SCN9A and monogenic human epilepsy disorders 

  Fasham, James; Crosby, Andrew H.; Baple, Emma L. (Public Library of Science, 2020-11-20)

  Many studies have demonstrated the clinical utility and importance of epilepsy gene panel testing to confirm the specific aetiology of disease, enable appropriate therapeutic interventions, and inform accurate family ...

• BICRA, a SWI/SNF Complex Member, Is Associated with BAF-Disorder Related Phenotypes in Humans and Model Organisms 

  Ellard, Sian; Stals, Karen (Elsevier Science, 2020-12-03)

  SWI/SNF-related intellectual disability disorders (SSRIDDs) are rare neurodevelopmental disorders characterized by developmental disability, coarse facial features, and fifth digit/nail hypoplasia that are caused by ...

• The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction 

  Kivuva, Emma (Nature Publishing Group, 2021-02)

  Purpose: Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better ...

• PRIM1 deficiency causes a distinctive primordial dwarfism syndrome 

  Rankin, Julia (HighWire, 2020-11-01)

  DNA replication is fundamental for cell proliferation in all organisms. Nonetheless, components of the replisome have been implicated in human disease, and here we report PRIM1 encoding the catalytic subunit of DNA primase ...

• Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C 

  Rankin, Julia (Oxford University Press, 2021-01-23)

  Context: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, ...

• Pathogenic germline variants in patients with features of hereditary renal cell carcinoma: Evidence for further locus heterogeneity 

  Castle, Bruce; Sansbury, Francis H (Wiley, 2021-01)

  Inherited renal cell carcinoma (RCC) is associated with multiple familial cancer syndromes but most individuals with features of non-syndromic inherited RCC do not harbor variants in the most commonly tested renal cancer ...

• Cerebral arteriopathy associated with heterozygous variants in the casitas B-lineage lymphoma gene 

  Rankin, Julia (Wolters Kluwer Health, Inc., 2020-06-10)

  Objective: To report a series of patients with cerebral arteriopathy associated with heterozygous variants in the casitas B-lineage lymphoma (CBL) gene and examine the functional role of the identified mutant Cbl protein. ...

• Inheritance of a paternal ABCC8 variant and maternal loss of heterozygosity at 11p15 retrospectively unmasks the etiology in a case of Congenital hyperinsulinism 

  Houghton, Jayne A. L. (Wiley, 2020-04-23)

  Advances in genomics and 18F-DOPA PET-CT imaging have transformed the management of infants with Congenital Hyperinsulinism. Preoperative diagnosis of focal hyperinsulinism permits limited pancreatectomy with improved ...

• Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants 

  Brewer, Carole (Nature Publishing Group, 2020-10)

  Purpose: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. Methods: ...

• Biallelic variants in PPP1R13L cause paediatric dilated cardiomyopathy 

  Robinson, H. K.; Mallin, L.; Mabin, David C.; Turner, Claire L.; Ellard, Sian (Wiley, 2020-10)

  Childhood dilated cardiomyopathy (DCM) is a leading cause of heart failure requiring cardiac transplantation and approximately 5% of cases result in sudden death. Knowledge of the underlying genetic cause can aid prognostication ...

• UKCGG Consensus Group guidelines for the management of patients with constitutional TP53 pathogenic variants 

  Gibson, Sarah (BMJ, 2020-06-22)

  Constitutional pathogenic variants in TP53 are associated with Li-Fraumeni syndrome or the more recently described heritable TP53-related cancer syndrome and are associated with increased lifetime risks of a wide spectrum ...

• Prostate Cancer Risk by BRCA2 Genomic Regions 

  Brewer, Carole (Elsevier Science, 2020-10)

  A BRCA2 prostate cancer cluster region (PCCR) was recently proposed (c.7914 to 3') wherein pathogenic variants (PVs) are associated with higher prostate cancer (PCa) risk than PVs elsewhere in the BRCA2 gene. Using a ...

• Late-onset Pseudoxanthoma Elasticum Associated with a Hypomorphic ABCC6 Variant 

  Tysoe, Carolyn; Caswell, Richard (Elsevier Science, 2020-10)

  Purpose: To describe patients with late-onset pseudoxanthoma elasticum (PXE) associated with a likely hypomorphic ABCC6 variant. Design: Retrospective observational case series. Methods: Clinical evaluation, multimodal ...

• Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations 

  Shaw-Smith, Charles (Wiley, 2020-06)

  Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS) is an autosomal dominant neurodevelopmental disorder caused by loss-of-function variants in NR2F1 and characterized by visual impairment, developmental delay, and ...

• Primrose syndrome: Characterization of the phenotype in 42 patients 

  Turnpenny, Peter (Wiley, 2020-06)

  Primrose syndrome (PS; MIM# 259050) is characterized by intellectual disability (ID), macrocephaly, unusual facial features (frontal bossing, deeply set eyes, down-slanting palpebral fissures), calcified external ears, ...

• Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome 

  Cleaver, Ruth (Oxford University Press, 2020-07-21)

  CTNND1 encodes the p120-catenin (p120) protein, which has a wide range of functions, including the maintenance of cell-cell junctions, regulation of the epithelial-mesenchymal transition and transcriptional signalling. Due ...

• Clinical spectrum of POLR3-related leukodystrophy caused by biallelic POLR1C pathogenic variants 

  Rankin, Julia (Wolters Kluwer Health, 2019-10-30)

  Objective: To determine the clinical, radiologic, and molecular characteristics of RNA polymerase III-related leukodystrophy (POLR3-HLD) caused by biallelic POLR1C pathogenic variants. Methods: A cross-sectional observational ...

• Dominant mutations of the Notch ligand Jagged1 cause peripheral neuropathy 

  Barwick, K. E. S.; Baple, Emma L.; Crosby, Andrew H. (American Society for Clinical Investigation, 2020-03-02)

  Notch signaling is a highly conserved intercellular pathway with tightly regulated and pleiotropic roles in normal tissue development and homeostasis. Dysregulated Notch signaling has also been implicated in human disease, ...

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