Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
AI Summary:
A family with three children was studied, and a heterozygous de novo nonsense SEC31A variant was detected. The children had different combinations of disorders, including gonadal dysgenesis, multiple pituitary hormone deficiencies, dysmorphic features, and developmental delay.AI Topics:
Purpose:
Disorders/differences of sex development (DSD) result from variants in many different human genes but, frequently, have no detectable molecular cause.
Methods:
Detailed clinical and genetic phenotyping was conducted on a family with three children. A Sec31a animal model and functional studies were used to investigate the significance of the findings.
Results:
By trio whole-exome DNA sequencing we detected a heterozygous de novo nonsense SEC31A variant, in three children of healthy non-consanguineous parents. The children had different combinations of disorders that included complete gonadal dysgenesis and multiple pituitary hormone deficiency. SEC31A encodes a component of the COPII coat protein complex, necessary for intracellular anterograde vesicle-mediated transport between the endoplasmic reticulum (ER) and Golgi. CRISPR-Cas9 targeted knockout of the orthologous Sec31a gene region resulted in early embryonic lethality in homozygous mice. mRNA expression of ER-stress genes ATF4 and CHOP was increased in the children, suggesting defective protein transport. The pLI score of the gene, from gnomAD data, is 0.02.
Conclusions:
SEC31A might underlie a previously unrecognised clinical syndrome comprising gonadal dysgenesis, multiple pituitary hormone deficiencies, dysmorphic features and developmental delay. However, a variant that remains undetected, in a different gene, may alternatively be causal in this family.
Tobias, Edward S.
Author
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listLucas-Herald, Angela K.
Author
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listSagar, Danielle
Author
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listMontezano, Augusto C.
Author
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listRios, Francisco J.
Author
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listDe Lucca Camargo, Livia
Author
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listHamilton, Graham
Author
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listGazdagh, Gabriella
Author
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listDiver, Louise A.
Author
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listWilliams, Nicola
Author
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listHerzyk, Pawel
Author
Elbassioni, Ali Ali Mohamed and Raheem, Anmar A. and Song, Jian and Johnston, Alexander S. and Trivett, Cara and Lin, Hong and Zhang, Haobo and Bradley, Ashley and Higgins, Erin and Mooney, Leanne and Koay, Yen Chin and O'Toole, Dylan and Herzyk, Pawel and Nixon, Colin and Blyth, Karen and O'Sullivan, John F. and Lang, Ninian N. and Berry, Colin and Braun, Thomas and Schiattarella, Gabriele G. and Giacca, Mauro and McBride, Martin W. and Nicklin, Stuart A. and Cameron, Ewan R. and Loughrey, Christopher M. and MacDonald, Eilidh A. (2025) Targeting Runx1 protects against heart failure with preserved ejection fraction. bioRxiv.
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listTouyz, Rhian M.
Author
Morrow, Andrew J. and Sykes, Robert and Saleh, Merna and Zahra, Baryab and MacIntosh, Alasdair and Kamdar, Anna and Bagot, Catherine and Bayes, Hannah K. and Blyth, Kevin G. and Bulluck, Heerajnarain and Carrick, David and Church, Colin and Corcoran, David and Findlay, Iain and Gibson, Vivienne and Gillespie, Lynsey and Grieve, Douglas and Hall Barrientos, Pauline and Ho, Antonia and Lang, Ninian N. and Lowe, David J. and Lennie, Vera and Macfarlane, Peter W. and Mayne, Kaitlin J. and Mark, Patrick B. and McConnachie, Alex and McGeoch, Ross and Nordin, Sabrina and Payne, Alexander and Rankin, Alastair J. and Robertson, Keith and Ryan, Nicola and Roditi, Giles and Sattar, Naveed and Stobo, David and Allwood-Spiers, Sarah and Touyz, Rhian M. and Veldtman, Gruschen and Weeden, Sarah and Weir, Robin and Watkins, Stuart and Welsh, Paul and Mangion, Kenneth and Berry, Colin (2024) Socioeconomic deprivation and illness trajectory in the Scottish population after COVID-19 hospitalization. Communications Medicine, 4: 32. ISSN 2730-664X
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listGreenfield, Andy
Author
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listMcGowan, Ruth
Author
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications listAhmed, S. Faisal
Author
Bohlen, Jonathan and Bagarić, Ivan and Vatovec, Taja and Ogishi, Masato and Ahmed, Syed F. and Cederholm, Axel and Buetow, Lori and Sobrino, Steicy and Le Floc’h, Corentin and Arango-Franco, Carlos A. and Seabra, Luis and Michelet, Marine and Barzaghi, Federica and Leardini, Davide and Saettini, Francesco and Vendemini, Francesca and Baccelli, Francesco and Catala, Albert and Gambineri, Eleonora and Veltroni, Marinella and Aguilar de la Red, Yurena and Rice, Gillian I. and Consonni, Filippo and Berteloot, Laureline and Largeaud, Laetitia and Conti, Francesca and Roullion, Cécile and Masson, Cécile and Bessot, Boris and Seeleuthner, Yoann and Le Voyer, Tom and Rinchai, Darawan and Rosain, Jérémie and Neehus, Anna-Lena and Erazo-Borrás, Lucia and Li, Hailun and Janda, Zarah and Cho, En-Jui and Muratore, Edoardo and Soudée, Camille and Lainé, Candice and Delabesse, Eric and Goulvestre, Claire and Ma, Cindy S. and Puel, Anne and Tangye, Stuart G. and André, Isabelle and Bole-Feysot, Christine and Abel, Laurent and Erlacher, Miriam and Zhang, Shen-Ying and Béziat, Vivien and Lagresle-Peyrou, Chantal and Six, Emmanuelle and Pasquet, Marlène and Alsina, Laia and Aiuti, Alessandro and Zhang, Peng and Crow, Yanick J. and Landegren, Nils and Masetti, Riccardo and Huang, Danny T. and Casanova, Jean-Laurent and Bustamante, Jacinta (2024) Autoinflammation in patients with leukocytic CBL loss of heterozygosity is caused by constitutive ERK-mediated monocyte activation. Journal of Clinical Investigation, 134 (20): e181604. ISSN 0021-9738
Dearlove, Emily L. and Chatrin, Chatrin and Buetow, Lori and Ahmed, Syed F. and Schmidt, Tobias and Bushell, Martin and Smith, Brian O. and Huang, Danny T. (2024) DTX3L ubiquitin ligase ubiquitinates single-stranded nucleic acids. eLife, 13: RP98070. ISSN 2050-084X
Tobias, Edward S. and Lucas-Herald, Angela K. and Sagar, Danielle and Montezano, Augusto C. and Rios, Francisco J. and De Lucca Camargo, Livia and Hamilton, Graham and Gazdagh, Gabriella and Diver, Louise A. and Williams, Nicola and Herzyk, Pawel and Touyz, Rhian M. and Greenfield, Andy and McGowan, Ruth and Ahmed, S. Faisal (2024) SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis. Endocrine, 84. pp. 345-349. ISSN 1355-008X
See full publications list