• Biallelic variants in COPB1 cause a novel, severe intellectual disability syndrome with cataracts and variable microcephaly. 

  Macken, William L.; Godwin, Annie; Wheway, Gabrielle; Stals, Karen; Nazlamova, Liliya; Ellard, Sian; Alfares, Ahmed; Aloraini, Taghrid; AlSubaie, Lamia; Alfadhel, Majid; Alajaji, Sulaiman; Wai, Htoo A.; Self, Jay; Douglas, Andrew G. L.; Kao, Alexander P.; Guille, Matthew; Baralle, Diana (BioMed Central, 2021-02-25)

  BACKGROUND: Coat protein complex 1 (COPI) is integral in the sorting and retrograde trafficking of proteins and lipids from the Golgi apparatus to the endoplasmic reticulum (ER). In recent years, coat proteins have been ...

• A second report of recessive type COL4A1-related disorder: a novel homozygous missense variant. 

  Sabir, Ataf H.; Singh, Ananya; Elley, George; Wassemer, Evangeline; Foster, Katharine; Sloman, Melissa; Lim, Derek (Wolters Kluwer, 2021-04-01)

• An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy. 

  Pagnamenta, Alistair T.; Kaiyrzhanov, Rauan; Zou, Yaqun; Da'as, Sahar I.; Maroofian, Reza; Donkervoort, Sandra; Dominik, Natalia; Lauffer, Marlen; Ferla, Matteo P.; Orioli, Andrea; Giess, Adam; Tucci, Arianna; Beetz, Christian; Sedghi, Maryam; Ansari, Behnaz; Barresi, Rita; Basiri, Keivan; Cortese, Andrea; Elgar, Greg; Fernandez-Garcia, Miguel A.; Yip, Janice; Foley, A. Reghan; Gutowski, Nicholas; Jungbluth, Heinz; Lassche, Saskia; Lavin, Tim; Marcelis, Carlo; Marks, Peter; Marini-Bettolo, Chiara; Medne, Livija; Moslemi, Ali-Reza; Sarkozy, Anna; Reilly, Mary M.; Muntoni, Francesco; Millan, Francisca; Muraresku, Colleen C.; Need, Anna C.; Nemeth, Andrea H.; Neuhaus, Sarah B.; Norwood, Fiona; O'Donnell, Marie; O'Driscoll, Mary; Rankin, Julia; Yum, Sabrina W.; Zolkipli-Cunningham, Zarazuela; Brusius, Isabell; Wunderlich, Gilbert; Karakaya, Mert; Wirth, Brunhilde; Fakhro, Khalid A.; Tajsharghi, Homa; Bönnemann, Carsten G.; Taylor, Jenny C.; Houlden, Henry (Oxford University Press, 2021-03-03)

  The extracellular matrix comprises a network of macromolecules such as collagens, proteoglycans and glycoproteins. VWA1 (von Willebrand factor A domain containing 1) encodes a component of the extracellular matrix that ...

• Diagnostic RET genetic testing in 1,058 index patients: A UK centre perspective. 

  Fussey, Jonathan Mark; Smith, Joel Anthony; Cleaver, Ruth; Bowles, Christopher; Ellard, Sian; Vaidya, Bijay; Owens, Martina (Wiley, 2020-12-19)

  OBJECTIVE: Diagnostic germline RET analysis is offered to all patients with a diagnosis of medullary thyroid carcinoma (MTC), or other conditions associated with multiple endocrine neoplasia type 2 (MEN2) in the United ...

• Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial. 

  Dimopoulos, Meletios; Sanz, Ramon Garcia; Lee, Hui-Peng; Trneny, Marek; Varettoni, Marzia; Opat, Stephen; D'Sa, Shirley; Owen, Roger G.; Cull, Gavin; Mulligan, Stephen; Czyz, Jaroslaw; Castillo, Jorge J.; Motta, Marina; Siddiqi, Tanya; Gironella Mesa, Mercedes; Granell Gorrochategui, Miquel; Talaulikar, Dipti; Zinzani, Pier Luigi; Askari, Elham; Grosicki, Sebastian; Oriol, Albert; Rule, Simon; Kloczko, Janusz; Tedeschi, Alessandra; Buske, Christian; Leblond, Veronique; Trotman, Judith; Chan, Wai Y.; Michel, Jan; Schneider, Jingjing; Tan, Ziwen; Cohen, Aileen; Huang, Jane; Tam, Constantine S. (American Society of Hematology, 2020-12-08)

  Patients with Waldenström macroglobulinemia (WM) lacking activating mutations in the MYD88 gene (MYD88WT) have demonstrated relatively poor outcomes to ibrutinib monotherapy, with no major responses reported in a phase 2 ...

• 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 ...

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