Germline mutations in young-onset sporadic pituitary macroadenomas: a multigene panel analysis DOI Open Access
Leonor M. Gaspar, Catarina Gonçalves, Ema Nobre

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 4, 2024

Abstract Objective Mutations in several genes have been associated with familial forms of pituitary adenomas. Sporadic adenomas (i.e. no family history or coexistent endocrine tumours) are also occasionally found to result from germline mutations these genes, especially young patients larger tumours. The aim this study was determine the frequency young-onset sporadic macroadenomas. Methods A cohort 225 Portuguese macroadenomas diagnosed before age 40 years studied by whole exome sequencing (WES) followed analysis a virtual panel 29 that predisposition Results Pathogenic and likely pathogenic variants were identified 16 (7.1%) patients. affected AIP (n=4), PMS2 MEN1 (n=2), VHL CDH23 (n=1), MSH2 SDHB TP53 (n=1). In under ages 30 18 years, increased 9.0% 12.0%, respectively. Conclusion This is so far largest multigene We confirmed as most frequently involved gene, but uncovered rarer genetic causes adenomas, including first independent confirmation role gene. results may contribute better understanding landscape tumours help decide which include screening

Language: Английский

Illuminating the terminal nerve: Uncovering the link between GnRH‐1 neuron and olfactory development DOI
Enrico Amato, Ed Zandro M. Taroc, Paolo E. Forni

et al.

The Journal of Comparative Neurology, Journal Year: 2024, Volume and Issue: 532(3)

Published: March 1, 2024

Abstract During embryonic development, the olfactory placode (OP) generates migratory neurons, including pioneer cells of terminal nerve (TN), gonadotropin‐releasing hormone‐1 (GnRH‐1) and other uncharacterized neurons. Pioneer neurons from OP induce bulb (OB) morphogenesis. In mice, GnRH‐1 appear in system around mid‐gestation migrate via TN axons to different brain regions. The are crucial controlling hypothalamic‐pituitary‐gonadal axis. Kallmann syndrome is characterized by impaired defective OBs, secretion GnRH‐1, infertility. precise mechanistic link between development remains unclear. Studies humans mice highlight importance prokineticin‐2/prokineticin‐receptor‐2 (Prokr2) signaling pathway OB morphogenesis neuronal migration. Prokr2 loss‐of‐function mutations can cause (KS), hence represents a unique model decipher olfactory/GnRH‐1 connection. We discovered that expressed during critical period neuron formation, migration, induction Single‐cell RNA sequencing identified formed distinct express multiple genes associated with KS. Our study suggests aberrant pioneer/TN might KS spectrum.

Language: Английский

Citations

6
Unlocking the Genetic Secrets of Acromegaly: Exploring the Role of Genetics in a Rare Disorder DOI Creative Commons

Ioana Balinisteanu,

Lavinia Caba, Andreea Florea

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(8), P. 9093 - 9121

Published: Aug. 20, 2024

Acromegaly is a rare endocrine disorder characterized by the excessive production of growth hormone (GH) in adulthood. Currently, it understood that certain pituitary neuroendocrine tumors (PitNETs) exhibit hereditary predisposition. These tumors’ genetic patterns fall into two categories: isolated and syndromic tumors. The forms are molecular defects predispose exclusively to PitNETs, including familial adenomas (FIPAs) sporadic not All categories involve either germline or somatic mutations, both, each associated with varying levels penetrance different phenotypes. This highlights importance testing need for more comprehensive view whole disease. Despite availability multiple treatment options, diagnosis often occurs after several years, management still difficult. Early detection intervention crucial preventing complications enhancing quality life affected individuals. review aims elucidate molecular, clinical, histological characteristics GH-secreting providing insights their prevalence, nuances, benefits type acromegaly.

Language: Английский

Citations

3
Germline genetic variants in young-onset sporadic pituitary macroadenomas: A multigene panel analysis DOI Creative Commons
Leonor M. Gaspar, Catarina Gonçalves, Ema Nobre

et al.

Journal of Clinical & Translational Endocrinology, Journal Year: 2025, Volume and Issue: unknown, P. 100389 - 100389

Published: April 1, 2025

Mutations in several genes have been associated with familial forms of pituitary adenomas. Sporadic adenomas (i.e. no family history or coexistent endocrine tumours) are also occasionally found to result from germline mutations these genes, especially young patients larger tumours. The aim this study was determine the frequency young-onset sporadic macroadenomas. A cohort 225 Portuguese macroadenomas diagnosed before age 40 years studied by whole exome sequencing (WES) followed analysis a virtual panel 29 that predisposition Pathogenic and likely pathogenic variants were identified 16 (7.1 %) patients. affected AIP (n = 4), PMS2 MEN1 2), VHL CDH23 1), MSH2 SDHB TP53 1). In under ages 30 18 years, increased 9.0 % 12.0 %, respectively. This is so far largest multigene We confirmed as most frequently involved gene, but uncovered rarer genetic causes results may contribute better understanding landscape tumours help decide which include screening

Language: Английский

Citations

0
Genetic Disorders of the Pituitary Gland DOI
Reed E. Pyeritz

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 455 - 493

Published: Nov. 15, 2024

Language: Английский

Citations

1
Illuminating the Terminal Nerve: Uncovering the Link between GnRH-1 and Olfactory Development DOI Open Access
Enrico Amato, Ed Zandro M. Taroc, Paolo E. Forni

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 3, 2023

Abstract During embryonic development, the olfactory placode (OP) generates migratory neurons, including pioneer cells of terminal nerve (TN), Gonadotropin-releasing hormone-1 (GnRH-1) and other uncharacterized neurons. Pioneer neurons from induce bulb morphogenesis. In mice, GnRH-1 appear in system around mid-gestation migrate via axons to different brain regions. The are crucial controlling hypothalamic-pituitary-gonadal (HPG) axis. Kallmann syndrome is characterized by impaired defective bulbs, secretion GnRH-1, infertility. precise mechanistic link between development remains unclear. Studies humans mice highlight importance Prokineticin-2/Prokineticin-Receptor-2 (Prokr2) signaling pathway morphogenesis neuronal migration. Prokr2 loss-of-function mutations can cause syndrome, hence represents a unique model decipher olfactory/GnRH-1 connection. We discovered that expressed TN during critical period neuron formation, migration, induction Single-cell RNA sequencing identified formed distinct express multiple genes associated with KS. Our study suggests aberrant pioneer/TN might KS spectrum. Key Points 1) or play role initiating bulbs. found Prokineticin Receptor-2 gene, pioneer/terminal 2) genetically traced, isolated, conducted on rodents. This analysis revealed significant enrichment gene expression related syndrome. 3) indicates investigation Pioneer/terminal should be pivotal focal point for comprehending developmental defects affecting systems.

Language: Английский

Citations

2
Diagnosis and Management of Acromegaly: A Consensus Statement of the Pituitary Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism DOI Creative Commons
Luís Cardoso, Pedro Marques, Maria Teresa Pereira

et al.

Deleted Journal, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 30

Published: Sept. 28, 2024

Acromegaly is characterised by hypersecretion of growth hormone and presents diagnostic therapeutic challenges that require consensus guidelines for effective management. The Pituitary Study Group the Portuguese Society Endocrinology, Diabetes Metabolism used a modified Delphi methodology to develop recommendations diagnosis management acromegaly. A multidisciplinary panel experts in acromegaly collaborated through this process establish consensus-based statements. authors did not receive any corporate funding or remuneration. employed achieve these included literature review specific topics, development statements, survey interactive discussions, subsequent comprehensive analysis results converge on key statements diagnosis, treatment, monitoring strategies. By synthesising available evidence integrating expert opinion, document offers valuable insights healthcare professionals, facilitating timely personalised treatment strategies developed teams, enhanced patient care.

Language: Английский

Citations

0
Germline mutations in young-onset sporadic pituitary macroadenomas: a multigene panel analysis DOI Open Access
Leonor M. Gaspar, Catarina Gonçalves, Ema Nobre

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 4, 2024

Abstract Objective Mutations in several genes have been associated with familial forms of pituitary adenomas. Sporadic adenomas (i.e. no family history or coexistent endocrine tumours) are also occasionally found to result from germline mutations these genes, especially young patients larger tumours. The aim this study was determine the frequency young-onset sporadic macroadenomas. Methods A cohort 225 Portuguese macroadenomas diagnosed before age 40 years studied by whole exome sequencing (WES) followed analysis a virtual panel 29 that predisposition Results Pathogenic and likely pathogenic variants were identified 16 (7.1%) patients. affected AIP (n=4), PMS2 MEN1 (n=2), VHL CDH23 (n=1), MSH2 SDHB TP53 (n=1). In under ages 30 18 years, increased 9.0% 12.0%, respectively. Conclusion This is so far largest multigene We confirmed as most frequently involved gene, but uncovered rarer genetic causes adenomas, including first independent confirmation role gene. results may contribute better understanding landscape tumours help decide which include screening

Language: Английский

Citations

0