Most recent papers in the journal European Journal of Human Genetics : EJHG

#1

JOURNAL ARTICLE

Balancing the rights of the pre-symptomatic child to be found with the risk of harm to others from the screening process.

Anneke Lucassen, Rachel Horton

No abstract text is available yet for this article.

39215146

August 30, 2024: European Journal of Human Genetics: EJHG

#2

JOURNAL ARTICLE

Becoming agents for genomic change: genetic counsellors' views of patient care and implementation influences when genomics is mainstreamed.

Trang Thu Do, Melissa Martyn, Belinda McClaren, Alison McEwen, Clara Gaff

Genetic counsellors (GCs) across the world are increasingly transitioning beyond clinical genetics services to meet the growing demands for genomic healthcare. This presents a unique opportunity for GCs to be 'genomic change agents' as they work in alternative models of care. Through various innovative models of mainstream care funded through a change program, we explored the views of GCs regarding their position as 'genomic change agents' and what may hinder or drive the success of their evolving roles. Guided by the Diffusion of Innovation Theory, we conducted qualitative interviews with all twelve GCs employed by the change program in different models of providing genomics across five specialties in Australia...

39210048

August 29, 2024: European Journal of Human Genetics: EJHG

#3

JOURNAL ARTICLE

Autosomal dominant stromal corneal dystrophy associated with a SPARCL1 missense variant.

Freddie L Braddock, Jessica C Gardner, Nihar Bhattacharyya, Beatriz Sanchez-Pintado, Marcos Costa, Christina Zarouchlioti, Anita Szabo, Petra Lišková, Michael E Cheetham, Robert D Young, Caroline Thaung, Alice E Davidson, Stephen J Tuft, Alison J Hardcastle

Corneal dystrophies are phenotypically and genetically heterogeneous, often resulting in visual impairment caused by corneal opacification. We investigated the genetic cause of an autosomal dominant corneal stromal dystrophy in a pedigree with eight affected individuals in three generations. Affected individuals had diffuse central stromal opacity, with reduced visual acuity in older family members. Histopathology of affected cornea tissue removed during surgery revealed mild stromal textural alterations with alcianophilic deposits...

39169229

August 21, 2024: European Journal of Human Genetics: EJHG

#4

JOURNAL ARTICLE

Novel fetal phenotype of TAF8 deficiency.

Golan Nadav, Marwan Odeh, Aviv Mesika, Yael Abarbanel Har-Tal, Moshe Goldfeld, Tania Zalatkin, Alejandro Livoff, Raghad Jeris Khoury, Inshirah Sgayer, Liat Ben-Sira, Limor Kalfon, Tzipora C Falik-Zaccai

TAF8 is part of the transcription factor TFIID complex. TFIID is crucial for recruiting the transcription factor complex containing RNA polymerase II. TAF8 deficiency was recently reported as causing a severe neurodevelopmental disorder in eight patients. We have ascertained three Muslim Arab couples with fetal brain malformations. Clinical, imaging, pathological, biochemical, and molecular analyses were performed. Pre-natal ultrasound performed in four pregnancies revealed massive cerebellar atrophy, microcephaly, cerebral and corpus callosum (CC) anomalies...

39169228

August 21, 2024: European Journal of Human Genetics: EJHG

#5

JOURNAL ARTICLE

Description and first insights on a large genomic biobank of lung transplantation.

Simon Brocard, Martin Morin, Nayane Dos Santos Brito Silva, Benjamin Renaud-Picard, Benjamin Coiffard, Xavier Demant, Loïc Falque, Jérome Le Pavec, Antoine Roux, Thomas Villeneuve, Christiane Knoop, Jean-François Mornex, Mathilde Salpin, Véronique Boussaud, Olivia Rousseau, Vincent Mauduit, Axelle Durand, Antoine Magnan, Pierre-Antoine Gourraud, Nicolas Vince, Mario Südholt, Adrien Tissot, Sophie Limou

The main limitation to long-term lung transplant (LT) survival is chronic lung allograft dysfunction (CLAD), which leads to irreversible lung damage and significant mortality. Individual factors can impact CLAD, but no large genetic investigation has been conducted to date. We established the multicentric Genetic COhort in Lung Transplantation (GenCOLT) biobank from a rich and homogeneous sub-part of COLT cohort. GenCOLT collected DNA, high-quality GWAS (genome-wide association study) genotyping and robust HLA data for donors and recipients to supplement COLT clinical data...

39164465

August 20, 2024: European Journal of Human Genetics: EJHG

#6

JOURNAL ARTICLE

Should the scope of NIPT be limited by a 'threshold of seriousness'?

Michelle Taylor-Sands, Molly Johnston, Catherine Mills

Non-invasive prenatal testing (NIPT) has the potential to screen for a wider range of genetic conditions than is currently possible at an early stage of pregnancy and with minimal risks. As such, there have been calls to apply a 'threshold of seriousness' to limit the scope of conditions being tested. This approach is based on concerns about society at large and the potential impact on specific groups within it. In this paper, we argue that limiting the scope of NIPT using the criterion of 'seriousness' is arbitrary, potentially stigmatises certain disabilities over others and fails to respect reproductive autonomy...

39152297

August 16, 2024: European Journal of Human Genetics: EJHG

#7

JOURNAL ARTICLE

Negotiating 'severity' in plain sight.

Aviad Raz

No abstract text is available yet for this article.

39143346

August 14, 2024: European Journal of Human Genetics: EJHG

#8

COMMENT

POT1 clinical risk management is an open question.

Mandy L Ballinger, David M Thomas

No abstract text is available yet for this article.

39134768

August 13, 2024: European Journal of Human Genetics: EJHG

#9

JOURNAL ARTICLE

Genomic sequencing in newborn screening: balancing consent with the right of the asymptomatic at-risk child to be found.

Bartha Maria Knoppers, Ana Eliza Bonilha, Anne-Marie Laberge, Arzoo Ahmed, Ainsley J Newson

In this paper, we explore key aspects of the complex ethical and legal landscape surrounding consent in the context of incorporating genomic sequencing into existing newborn bloodspot screening programs. In particular, we consider the potential impact of genomic sequencing on the health rights of the child in relation to existing consent practices in newborn screening. We begin with an introduction to newborn screening programs and their population health goals. We then discuss public health ethics as a rationale underpinning newborn screening before turning to consent...

39134767

August 12, 2024: European Journal of Human Genetics: EJHG

#10

JOURNAL ARTICLE

Ancestral genetic components are consistently associated with the complex trait landscape in European biobanks.

Vasili Pankratov, Massimo Mezzavilla, Serena Aneli, Ivan A Kuznetsov, Daniela Fusco, James F Wilson, Mait Metspalu, Paolo Provero, Luca Pagani, Davide Marnetto

The genetic structure in Europe was mostly shaped by admixture between the Western Hunter-Gatherers, Early European Farmers and Steppe Bronze Age ancestral components. Such structure is regarded as a confounder in GWAS and follow-up studies, and gold-standard methods exist to correct for it. However, it is still poorly understood to which extent these ancestral components contribute to complex trait variation in present-day Europe. In this work we harness the UK Biobank to address this question. By extensive demographic simulations, exploiting data on siblings and incorporating previous results we obtained from the Estonian Biobank, we carefully evaluate the significance and scope of our findings...

39127804

August 10, 2024: European Journal of Human Genetics: EJHG

#11

REVIEW

Unpacking the notion of "serious" genetic conditions: towards implementation in reproductive decision-making?

Erika Kleiderman, Felicity Boardman, Ainsley J Newson, Anne-Marie Laberge, Bartha Maria Knoppers, Vardit Ravitsky

The notion of a "serious" genetic condition is commonly used in clinical contexts, laws, and policies to define and delineate both the permissibility of and, access to, reproductive genomic technologies. Yet, the notion lacks conceptual and operational clarity, which can lead to its inconsistent appraisal and application. A common understanding of the relevant considerations of "serious" is lacking. This article addresses this conceptual gap. We begin by outlining existing distinctions around the notion of "serious" that will factor into its appraisal and need to be navigated, in the context of prenatal testing and the use of reproductive genomic technologies...

39127803

August 10, 2024: European Journal of Human Genetics: EJHG

#12

JOURNAL ARTICLE

Late-onset tumors in rhabdoid tumor predisposition syndrome type-1 (RTPS1) and implications for surveillance.

Yoshiko Nakano, Meryl Acker, Harriet Druker, Kalene van Engelen, M Stephen Meyn, Jonathan D Wasserman, Rosemarie E Venier, Catherine Goudie, Ana Stosic, Annie Huang, Mary-Louise C Greer, David Malkin, Anita Villani, Bailey Gallinger

Rhabdoid tumor predisposition syndrome type-1 (RTPS1) is characterized by germline pathogenic variants in SMARCB1 and development of INI1-deficient rhabdoid tumors in early childhood. Due to its poor prognosis, the risk of subsequent tumor development and the impact of surveillance at later ages are poorly understood. We retrospectively reviewed individuals referred to the Cancer Genetics Program at The Hospital for Sick Children for SMARCB1 genetic testing and/or surveillance for RTPS1. In addition, to explore characteristics of late-onset tumors in RTPS1, a literature review was conducted...

39117932

August 8, 2024: European Journal of Human Genetics: EJHG

#13

JOURNAL ARTICLE

Assessment of ability of AlphaMissense to identify variants affecting susceptibility to common disease.

David Curtis

An important issue in the analysis of rare variant association studies is the ability to annotate nonsynonymous variants in terms of their likely importance as affecting protein function. To address this, AlphaMissense was recently released and was shown to have good performance using benchmarks based on variants causing severe disease and on functional assays. Here, we assess the performance of AlphaMissense across 18 genes which had previously demonstrated association between rare coding variants and hyperlipidaemia, hypertension or type 2 diabetes...

39097650

August 3, 2024: European Journal of Human Genetics: EJHG

#14

Correction: EMQN best practice guidelines for genetic testing in hereditary breast and ovarian cancer.

Trudi McDevitt, Miranda Durkie, Norbert Arnold, George J Burghel, Samantha Butler, Kathleen B M Claes, Peter Logan, Rachel Robinson, Katie Sheils, Nicola Wolstenholme, Helen Hanson, Clare Turnbull, Stacey Hume

No abstract text is available yet for this article.

39095510

August 2, 2024: European Journal of Human Genetics: EJHG

#15

JOURNAL ARTICLE

Colorectal cancer risk stratification using a polygenic risk score in symptomatic primary care patients-a UK Biobank retrospective cohort study.

Bethan Mallabar-Rimmer, Samuel W D Merriel, Amy P Webster, Leigh Jackson, Andrew R Wood, Matthew Barclay, Jessica Tyrrell, Katherine S Ruth, Christina Thirlwell, Richard Oram, Michael N Weedon, Sarah E R Bailey, Harry D Green

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Accurate cancer risk assessment approaches could increase rates of early CRC diagnosis, improve health outcomes for patients and reduce pressure on diagnostic services. The faecal immunochemical test (FIT) for blood in stool is widely used in primary care to identify symptomatic patients with likely CRC. However, there is a 6-16% noncompliance rate with FIT in clinic and ~90% of patients over the symptomatic 10 µg/g test threshold do not have CRC...

39090236

August 1, 2024: European Journal of Human Genetics: EJHG

#16

REVIEW

ERN GENTURIS clinical practice guidelines for the diagnosis, surveillance and management of people with Birt-Hogg-Dubé syndrome.

Marianne Geilswijk, Maurizio Genuardi, Emma R Woodward, Katie Nightingale, Jazzmin Huber, Mia Gebauer Madsen, Dieke Liekelema-van der Heij, Ian Lisseman, Jenny Marlé-Ballangé, Cormac McCarthy, Fred H Menko, R Jeroen A van Moorselaar, Elzbieta Radzikowska, Stéphane Richard, Neil Rajan, Mette Sommerlund, Maria T A Wetscherek, Nataliya Di Donato, Eamonn R Maher, Joan Brunet

Birt-Hogg-Dubé syndrome (BHD syndrome) is an autosomal dominant multisystem disorder with variable expression due to pathogenic constitutional variants in the FLCN gene. Patients with BHD syndrome are predisposed to benign cutaneous fibrofolliculomas/trichodischomas, pulmonary cysts with an associated risk of spontaneous pneumothorax, and renal cell carcinoma. A requirement for updated International consensus recommendations for the diagnosis and management of BHD syndrome was identified. Based on a comprehensive literature review and expert consensus within the fields of respiratory medicine, urology, radiology, dermatology, clinical oncology and clinical genetics, updated recommendations for diagnosis, surveillance and management in BHD syndrome were developed...

39085584

July 31, 2024: European Journal of Human Genetics: EJHG

#17

REVIEW

Bardet-Biedl syndrome improved diagnosis criteria and management: Inter European Reference Networks consensus statement and recommendations.

Hélène Dollfus, Marc R Lilien, Pietro Maffei, Alain Verloes, Jean Muller, Giacomo M Bacci, Metin Cetiner, Erica L T van den Akker, Monika Grudzinska Pechhacker, Francesco Testa, Didier Lacombe, Marijn F Stokman, Francesca Simonelli, Aurélie Gouronc, Amélie Gavard, Mieke M van Haelst, Jens Koenig, Sylvie Rossignol, Carsten Bergmann, Miriam Zacchia, Bart P Leroy, Héléna Mosbah, Albertien M Van Eerde, Djalila Mekahli, Aude Servais, Christine Poitou, Diana Valverde

Four European Reference Networks (ERN-EYE, ERKNet, Endo-ERN, ERN-ITHACA) have teamed up to establish a consensus statement and recommendations for Bardet-Biedl syndrome (BBS). BBS is an autosomal recessive ciliopathy with at least 26 genes identified to date. The clinical manifestations are pleiotropic, can be observed in utero and will progress with age. Genetic testing has progressively improved in the last years prompting for a revision of the diagnostic criteria taking into account clinical Primary and Secondary features, as well as positive or negative molecular diagnosis...

39085583

July 31, 2024: European Journal of Human Genetics: EJHG

#18

Correction: STAC3 disorder: a common cause of congenital hypotonia in Southern African patients.

Fahmida Essop, Bronwyn Dillon, Felicity Mhlongo, Louisa Bhengu, Thirona Naicker, Lindsay Lambie, Liani Smit, Karen Fieggen, Anneline Lochan, Jessica Dawson, Phelelani Mpangase, Marc Hauptfleisch, Gail Scher, Odirile Tabane, Marelize Immelman, Michael Urban, Amanda Krause

No abstract text is available yet for this article.

39080471

July 30, 2024: European Journal of Human Genetics: EJHG

#19

Correction: Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals.

Dana E Layo-Carris, Emily E Lubin, Annabel K Sangree, Kelly J Clark, Emily L Durham, Elizabeth M Gonzalez, Sarina Smith, Rajesh Angireddy, Xiao Min Wang, Erin Weiss, Annick Toutain, Roberto Mendoza-Londono, Lucie Dupuis, Nadirah Damseh, Danita Velasco, Irene Valenzuela, Marta Codina-Solà, Catherine Ziats, Jaclyn Have, Katie Clarkson, Dora Steel, Manju Kurian, Katy Barwick, Diana Carrasco, Aditi I Dagli, M J M Nowaczyk, Miroslava Hančárová, Šárka Bendová, Darina Prchalova, Zdeněk Sedláček, Alica Baxová, Catherine Bearce Nowak, Jessica Douglas, Wendy K Chung, Nicola Longo, Konrad Platzer, Chiara Klöckner, Luisa Averdunk, Dagmar Wieczorek, Ilona Krey, Christiane Zweier, Andre Reis, Tugce Balci, Marleen Simon, Hester Y Kroes, Antje Wiesener, Georgia Vasileiou, Nikolaos M Marinakis, Danai Veltra, Christalena Sofocleous, Konstantina Kosma, Joanne Traeger Synodinos, Konstantinos A Voudris, Marie-Laure Vuillaume, Paul Gueguen, Nicolas Derive, Estelle Colin, Clarisse Battault, Billie Au, Martin Delatycki, Mathew Wallis, Lyndon Gallacher, Fatma Majdoub, Noor Smal, Sarah Weckhuysen, An-Sofie Schoonjans, R Frank Kooy, Marije Meuwissen, Benjamin T Cocanougher, Kathryn Taylor, Carolyn E Pizoli, Marie T McDonald, Philip James, Elizabeth R Roeder, Rebecca Littlejohn, Nicholas A Borja, Willa Thorson, Kristine King, Radka Stoeva, Manon Suerink, Esther Nibbeling, Stephanie Baskin, Gwenaël L E Guyader, Julie Kaplan, Candace Muss, Deanna Alexis Carere, Elizabeth J K Bhoj, Laura M Bryant

No abstract text is available yet for this article.

39060653

July 26, 2024: European Journal of Human Genetics: EJHG

#20

JOURNAL ARTICLE

Are employees ready to engage in genetic cancer risk assessment in the workplace setting?

Isabelle R Chandler, Jesse T Brewer, Muhammad Danyal Ahsan, Tamar Nicole Soussana, Emily M Webster, Michelle Primiano, Ravi N Sharaf, Melissa K Frey

No abstract text is available yet for this article.

39043975

July 23, 2024: European Journal of Human Genetics: EJHG