• THUMPD1 bi-allelic variants cause loss of tRNA acetylation and a syndromic neurodevelopmental disorder 

  Broly, M.; Polevoda, B. V.; Awayda, K. M.; Tong, N.; Lentini, J.; Besnard, T.; Deb, W.; O'Rourke, D.; Baptista, J.; Ellard, S.; Almannai, M.; Hashem, M.; Abdulwahab, F.; Shamseldin, H.; Al-Tala, S.; Alkuraya, F. S.; Leon, A.; van Loon, R. L. E.; Ferlini, A.; Sanchini, M.; Bigoni, S.; Ciorba, A.; van Bokhoven, H.; Iqbal, Z.; Al-Maawali, A.; Al-Murshedi, F.; Ganesh, A.; Al-Mamari, W.; Lim, S. C.; Pais, L. S.; Brown, N.; Riazuddin, S.; Bézieau, S.; Fu, D.; Isidor, B.; Cogné, B.; O'Connell, M. R. (Cell Press, 2022-02-11)

  Covalent tRNA modifications play multi-faceted roles in tRNA stability, folding, and recognition, as well as the rate and fidelity of translation, and other cellular processes such as growth, development, and stress ...

• Evaluation of Evidence for Pathogenicity Demonstrates that BLK, KLF11 and PAX4 Should not be Included in Diagnostic Testing for MODY 

  Laver, T. W.; Wakeling, M. N.; Knox, O.; Colclough, K.; Wright, C. F.; Ellard, S.; Hattersley, A. T.; Weedon, M. N.; Patel, K. A. (American Diabetes Association, 2022-02-02)

  Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant form of monogenic diabetes, reported to be caused by variants in 16 genes. Concern has been raised about whether variants in BLK (MODY11), KLF11 (MODY7) ...

• X-linked Ohdo syndrome due to a novel MED12 variant detected by Rapid Exome Sequencing 

  McDermott, H.; Garikapati, V.; Baptista, J.; Gowda, H.; Naik, S. (Wolters Kluwer, 2022-04-01)

• SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile 

  Al-Jawahiri, R.; Foroutan, A.; Kerkhof, J.; McConkey, H.; Levy, M.; Haghshenas, S.; Rooney, K.; Turner, J.; Shears, D.; Holder, M.; Lefroy, H.; Castle, B.; Reis, L. M.; Semina, E. V.; Lachlan, K.; Chandler, K.; Wright, T.; Clayton-Smith, J.; Hug, F. P.; Pitteloud, N.; Bartoloni, L.; Hoffjan, S.; Park, S. M.; Thankamony, A.; Lees, M.; Wakeling, E.; Naik, S.; Hanker, B.; Girisha, K. M.; Agolini, E.; Giuseppe, Z.; Alban, Z.; Tessarech, M.; Keren, B.; Afenjar, A.; Zweier, C.; Reis, A.; Smol, T.; Tsurusaki, Y.; Nobuhiko, O.; Sekiguchi, F.; Tsuchida, N.; Matsumoto, N.; Kou, I.; Yonezawa, Y.; Ikegawa, S.; Callewaert, B.; Freeth, M.; Kleinendorst, L.; Donaldson, A.; Alders, M.; De Paepe, A.; Sadikovic, B.; McNeill, A. (Nature, 2022-03-24)

  PURPOSE: This study aimed to undertake a multidisciplinary characterization of the phenotype associated with SOX11 variants. METHODS: Individuals with protein altering variants in SOX11 were identified through exome and ...

• Clinical and genetic heterogeneity of HNF4A/HNF1A mutations in a multicentre paediatric cohort with hyperinsulinaemic hypoglycaemia 

  McGlacken-Byrne, S. M.; Mohammad, J. K.; Conlon, N.; Gubaeva, D.; Siersbæk, J.; Schou, A. J.; Demirbilek, H.; Dastamani, A.; Houghton, J. A. L.; Brusgaard, K.; Melikyan, M.; Christesen, H.; Flanagan, S. E.; Murphy, N. P.; Shah, P. (BioScientifica, 2022-02-22)

  OBJECTIVE: The phenotype mediated by HNF4A/HNF1A mutations is variable and includes diazoxide-responsive hyperinsulinaemic hypoglycaemia (HH) and maturity-onset diabetes of the young (MODY). DESIGN: We characterised an ...

• Biallelic variants in TRAPPC10 cause a microcephalic TRAPPopathy disorder in humans and mice 

  Rawlins, L. E.; Almousa, H.; Khan, S.; Collins, S. C.; Milev, M. P.; Leslie, J.; Saint-Dic, D.; Khan, V.; Hincapie, A. M.; Day, J. O.; McGavin, L.; Rowley, C.; Harlalka, G. V.; Vancollie, V. E.; Ahmad, W.; Lelliott, C. J.; Gul, A.; Yalcin, B.; Crosby, A. H.; Sacher, M.; Baple, E. L. (PLoS One, 2022-03-01)

  The highly evolutionarily conserved transport protein particle (TRAPP) complexes (TRAPP II and III) perform fundamental roles in subcellular trafficking pathways. Here we identified biallelic variants in TRAPPC10, a component ...

• Consolidation of the clinical and genetic definition of a SOX4-related neurodevelopmental syndrome 

  Angelozzi, M.; Karvande, A.; Molin, A. N.; Ritter, A. L.; Leonard, J. M. M.; Savatt, J. M.; Douglass, K.; Myers, S. M.; Grippa, M.; Tolchin, D.; Zackai, E.; Donoghue, S.; Hurst, A. C. E.; Descartes, M.; Smith, K.; Velasco, D.; Schmanski, A.; Crunk, A.; Tokita, M. J.; de Lange, I. M.; van Gassen, K.; Robinson, H.; Guegan, K.; Suri, M.; Patel, C.; Bournez, M.; Faivre, L.; Tran-Mau-Them, F.; Baker, J.; Fabie, N.; Weaver, K.; Shillington, A.; Hopkin, R. J.; Barge-Schaapveld, Dqcm; Ruivenkamp, C. A.; Bökenkamp, R.; Vergano, S.; Seco Moro, M. N.; Díaz de Bustamante, A.; Misra, V. K.; Kennelly, K.; Rogers, C.; Friedman, J.; Wigby, K. M.; Lenberg, J.; Graziano, C.; Ahrens-Nicklas, R. C.; Lefebvre, V. (BMJ, 2022-03-01)

  BACKGROUND: A neurodevelopmental syndrome was recently reported in four patients with SOX4 heterozygous missense variants in the high-mobility-group (HMG) DNA-binding domain. The present study aimed to consolidate clinical ...

• UK recommendations for SDHA germline genetic testing and surveillance in clinical practice 

  Hanson, H.; Durkie, M.; Lalloo, F.; Izatt, L.; McVeigh, T. P.; Cook, J. A.; Brewer, C.; Drummond, J.; Butler, S.; Cranston, T.; Casey, R.; Tan, T.; Morganstein, D.; Eccles, D. M.; Tischkowitz, M.; Turnbull, C.; Woodward, E. R.; Maher, E. R. (BMJ, 2022-03-08)

  SDHA pathogenic germline variants (PGVs) are identified in up to 10% of patients with paraganglioma and phaeochromocytoma and up to 30% with wild-type gastrointestinal stromal tumours. Most SDHA PGV carriers present with ...

• Evidence that the Ser192Tyr/Arg402Gln in cis Tyrosinase gene haplotype is a disease-causing allele in oculocutaneous albinism type 1B (OCA1B) 

  Lin, S.; Sanchez-Bretaño, A.; Leslie, J. S.; Williams, K. B.; Lee, H.; Thomas, N. S.; Callaway, J.; Deline, J.; Ratnayaka, J. A.; Baralle, D.; Schmitt, M. A.; Norman, C. S.; Hammond, S.; Harlalka, G. V.; Ennis, S.; Cross, H. E.; Wenger, O.; Crosby, A. H.; Baple, E. L.; Self, J. E. (PubMed Central, 2022-01-13)

  Oculocutaneous albinism type 1 (OCA1) is caused by pathogenic variants in the TYR (tyrosinase) gene which encodes the critical and rate-limiting enzyme in melanin synthesis. It is the most common OCA subtype found in ...

• Glycated haemoglobin measurements from UK Biobank are different to those in linked primary care records: implications for combining biochemistry data from research studies and routine clinical care 

  Young, K. G.; McDonald, T. J.; Shields, B. M. (Oxford University Press, 2022-01-13)

• Improvements in Awareness and Testing Have Led to a Threefold Increase Over 10 Years in the Identification of Monogenic Diabetes in the U.K 

  Pang, L.; Colclough, K. C.; Shepherd, M. H.; McLean, J.; Pearson, E. R.; Ellard, S.; Hattersley, A. T.; Shields, B. M. (American Diabetes Association, 2022-01-21)

  OBJECTIVE: Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes. In 2009, >80% of U.K. cases were estimated to be misdiagnosed. Since then, there have been a number of initiatives to improve the ...

• Elucidating the clinical spectrum and molecular basis of HYAL2 deficiency 

  Fasham, J.; Lin, S.; Ghosh, P.; Radio, F. C.; Farrow, E. G.; Thiffault, I.; Kussman, J.; Zhou, D.; Hemming, R.; Zahka, K.; Chioza, B. A.; Rawlins, L. E.; Wenger, O. K.; Gunning, A. C.; Pizzi, S.; Onesimo, R.; Zampino, G.; Barker, E.; Osawa, N.; Rodriguez, M. C.; Neuhann, T. M.; Zackai, E. H.; Keena, B.; Capasso, J.; Levin, A. V.; Bhoj, E.; Li, D.; Hakonarson, H.; Wentzensen, I. M.; Jackson, A.; Chandler, K. E.; Coban-Akdemir, Z. H.; Posey, J. E.; Banka, S.; Lupski, J. R.; Sheppard, S. E.; Tartaglia, M.; Triggs-Raine, B.; Crosby, A. H.; Baple, E. L. (Nature, 2021-11-30)

  PURPOSE: We previously defined biallelic HYAL2 variants causing a novel disorder in 2 families, involving orofacial clefting, facial dysmorphism, congenital heart disease, and ocular abnormalities, with Hyal2 knockout mice ...

• Natural history of NF1 c.2970_2972del p.(Met992del): confirmation of a low risk of complications in a longitudinal study 

  Forde, C.; Burkitt-Wright, E.; Turnpenny, P. D.; Haan, E.; Ealing, J.; Mansour, S.; Holder, M.; Lahiri, N.; Dixit, A.; Procter, A.; Pacot, L.; Vidaud, D.; Capri, Y.; Gerard, M.; Dollfus, H.; Schaefer, E.; Quelin, C.; Sigaudy, S.; Busa, T.; Vera, G.; Damaj, L.; Messiaen, L.; Stevenson, D. A.; Davies, P.; Palmer-Smith, S.; Callaway, A.; Wolkenstein, P.; Pasmant, E.; Upadhyaya, M. (Nature, 2021-12-13)

  Individuals with the three base pair deletion NM_000267.3(NF1):c.2970_2972del p.(Met992del) have been recognised to present with a milder neurofibromatosis type 1 (NF1) phenotype characterised by café-au-lait macules (CALs) ...

• Quantifying prediction of pathogenicity for within-codon concordance (PM5) using 7541 functional classifications of BRCA1 and MSH2 missense variants 

  Loong, L.; Cubuk, C.; Choi, S.; Allen, S.; Torr, B.; Garrett, A.; Loveday, C.; Durkie, M.; Callaway, A.; Burghel, G. J.; Drummond, J.; Robinson, R.; Berry, I. R.; Wallace, A.; Eccles, D. M.; Tischkowitz, M.; Ellard, S.; Ware, J. S.; Hanson, H.; Turnbull, C. (Nature, 2021-11-18)

  PURPOSE: Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical ...

• Persistence of clinically relevant levels of SARS-CoV2 envelope gene subgenomic RNAs in non-immunocompromised individuals 

  Davies, M.; Bramwell, L. R.; Jeffery, N.; Bunce, B.; Lee, B. P.; Knight, B.; Auckland, C.; Masoli, J. A.; Harries, L. W. (Elsevier, 2021-12-07)

  OBJECTIVES: This study aimed to evaluate the associations between COVID-19 severity and active viral load, and to characterize the dynamics of active SARS-CoV-2 clearance in a series of archival samples taken from patients ...

• Novel mutations in PDE6A and CDHR1 cause retinitis pigmentosa in Pakistani families 

  Dawood, M.; Lin, S.; Din, T. U.; Shah, I. U.; Khan, N.; Jan, A.; Marwan, M.; Sultan, K.; Nowshid, M.; Tahir, R.; Ahmed, A. N.; Yasin, M.; Baple, E. L.; Crosby, A. H.; Saleha, S. (International Journal of Ophthalmology Press, 2021-12-21)

  AIM: To investigate the genetic basis of autosomal recessive retinitis pigmentosa (arRP) in two consanguineous/ endogamous Pakistani families. METHODS: Whole exome sequencing (WES) was performed on genomic DNA samples of ...

• Expanding the phenotypic spectrum of ALDH18A1-related autosomal recessive cutis laxa with a description of novel neuroradiological findings 

  Pickwick, C.; Callewaert, B.; van Dijk, F.; Harris, J.; Wakeling, E.; Hay, E.; Yeo, M.; Chakrapani, A.; Baptista, J.; Moore, S.; Yoong, M.; Chatterjee, F.; Ghali, N. (Wolters Kluwer, 2021-12-24)

• Exploring Genotype: Phenotype Correlations at Baseline and at One Year for ET and PV Patients in the Majic Study 

  Saha, Chandan; Mead-Harvey, Carolyn; Mead, Adam J.; Boucher, Rebecca H.; Fox, Sonia; Ailts, Isaak; Yap, Christina; Jackson, Aimee E.; Ewing, Joanne; Coppell, Jason; Knapper, Steve; Drummond, Mark W.; Godfrey, Anna L.; Dueck, Amylou C.; Mesa, Ruben A.; Scherber, Robyn; McMullin, Mary Frances; Geyer, Holly L.; Harrison, Claire N. (Blood, 2021-11-23)

  The myeloproliferative neoplasms (MPN) polycythaemia vera (PV) and essential thrombocythaemia (ET) are associated with significant symptom burden with impaired quality of life (QoL). In the MAJIC study patients ...

• Further delineation of phenotypic spectrum of SCN2A-related disorder 

  Richardson, R.; Baralle, D.; Bennett, C.; Briggs, T.; Bijlsma, E. K.; Clayton-Smith, J.; Constantinou, P.; Foulds, N.; Jarvis, J.; Jewell, R.; Johnson, D. S.; McEntagart, M.; Parker, M. J.; Radley, J. A.; Robertson, L.; Ruivenkamp, C.; Rutten, J. W.; Tellez, J.; Turnpenny, P. D.; Wilson, V.; Wright, M.; Balasubramanian, M. (Wiley, 2021-12-11)

  SCN2A-related disorders include intellectual disability, autism spectrum disorder, seizures, episodic ataxia, and schizophrenia. In this study, the phenotype-genotype association in SCN2A-related disorders was further ...

• Systematic genetic testing for recessively inherited monogenic diabetes: a cross-sectional study in paediatric diabetes clinics 

  Patel, K. A.; Ozbek, M. N.; Yildiz, M.; Guran, T.; Kocyigit, C.; Acar, S.; Siklar, Z.; Atar, M.; Colclough, K.; Houghton, J.; Johnson, M. B.; Ellard, S.; Flanagan, S. E.; Cizmecioglu, F.; Berberoglu, M.; Demir, K.; Catli, G.; Bas, S.; Akcay, T.; Demirbilek, H.; Weedon, M. N.; Hattersley, A. T. (Springer, 2021-10-23)

  AIMS/HYPOTHESIS: Current clinical guidelines for childhood-onset monogenic diabetes outside infancy are mainly focused on identifying and testing for dominantly inherited, predominantly MODY genes. There are no systematic ...

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