Novel germline variants of CDKN1B and CDKN2C identified during screening for familial primary hyperparathyroidism.

Humans Germ-Line Mutation Hyperparathyroidism, Primary / diagnosis DNA Copy Number Variations DNA / genetics Germ Cells / pathology Neoplasms Multiple Endocrine Neoplasia Type 1 Cyclin-Dependent Kinase Inhibitor p27 / genetics Cyclin-Dependent Kinase Inhibitor p18 / genetics
Cyclin dependent kinase inhibitors Multiple endocrine neoplasia type 1 Multiple endocrine neoplasia type 4 Parathyroid Primary hyperparathyroidism

Journal

Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594

Informations de publication

Date de publication:
Apr 2023
Historique:
received: 18 03 2022
accepted: 22 10 2022
pubmed: 6 11 2022
medline: 22 3 2023
entrez: 5 11 2022
Statut: ppublish

Résumé

CDKN1B mutations were established as a cause of multiple endocrine neoplasia 4 (MEN4) syndrome in patients with MEN1 phenotype without a mutation in the MEN1 gene. In addition, variants in other cyclin-dependent kinase inhibitors (CDKIs) were found in some MEN1-like cases without the MEN1 mutation. We aimed to describe novel germline mutations of these genes in patients with primary hyperparathyroidism (PHPT). During genetic screening for familial hyperparathyroidism, three novel CDKIs germline mutations in three unrelated cases between January 2019 and November 2021 were identified. In this report, we describe clinical features, DNA sequence analysis, and familial segregation studies based on these patients and their relatives. Genome-wide DNA study of loss of heterozygosity (LOH), copy number variation (CNV), and p27/kip immunohistochemistry was performed on tumour samples. DNA screening was performed for atypical parathyroid adenomas in cases 1 and 2 and for cystic parathyroid adenoma and young age at diagnosis of PHPT in case 3. Genetic analysis identified likely pathogenic variants of CDKN1B in cases 1 and 2 and a variant of the uncertain significance of CDKN2C, with uniparental disomy in the tumour sample, in case 3. Neoplasm screening of probands showed other non-endocrine tumours in case 1 (colon adenoma with dysplasia and atypical lipomas) and case 2 (aberrant T-cell population) and a non-functional pituitary adenoma in case 3. Germline mutations in CDKIs should be included in gene panels for genetic testing of primary hyperparathyroidism. New germline variants here described can be added to the current knowledge.

Identifiants

DOI: 10.1007/s40618-022-01948-7 PMID: 36334246 PMC: PMC10023768
pubmed: 36334246
doi: 10.1007/s40618-022-01948-7
pii: 10.1007/s40618-022-01948-7
pmc: PMC10023768
doi:

Substances chimiques

DNA 9007-49-2
CDKN1B protein, human 0
Cyclin-Dependent Kinase Inhibitor p27 147604-94-2
CDKN2C protein, human 0
Cyclin-Dependent Kinase Inhibitor p18 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

829-840

Informations de copyright

© 2022. The Author(s).

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Auteurs

I Mazarico-Altisent (I)

Endocrinology and Nutrition Department, Parc Taulí University Hospital, Institut d'Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Parc Taulí 1, 08208, Sabadell, Barcelona, Spain. isamazarico@gmail.com.
ORCID: 0000-0001-9651-7650

I Capel (I)

Endocrinology and Nutrition Department, Parc Taulí University Hospital, Institut d'Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Parc Taulí 1, 08208, Sabadell, Barcelona, Spain.

N Baena (N)

Genetic Department, Parc Taulí University Hospital, Institut d'Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Parc Taulí 1, 08208, Sabadell, Barcelona, Spain.

M R Bella-Cueto (MR)

Pathology Department, Parc Taulí University Hospital, Institut d'Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Parc Taulí 1, 08208, Sabadell, Barcelona, Spain.

S Barcons (S)

Surgery Department, Parc Taulí University Hospital, Institut d'Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Parc Taulí 1, 08208, Sabadell, Barcelona, Spain.

X Guirao (X)

Surgery Department, Parc Taulí University Hospital, Institut d'Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Parc Taulí 1, 08208, Sabadell, Barcelona, Spain.

L Albert (L)

Endocrinology and Nutrition Department, Parc Taulí University Hospital, Institut d'Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Parc Taulí 1, 08208, Sabadell, Barcelona, Spain.

A Cano (A)

Endocrinology and Nutrition Department, Parc Taulí University Hospital, Institut d'Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Parc Taulí 1, 08208, Sabadell, Barcelona, Spain.

R Pareja (R)

Endocrinology and Nutrition Department, Parc Taulí University Hospital, Institut d'Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Parc Taulí 1, 08208, Sabadell, Barcelona, Spain.

A Caixàs (A)

Endocrinology and Nutrition Department, Parc Taulí University Hospital, Institut d'Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Parc Taulí 1, 08208, Sabadell, Barcelona, Spain.

M Rigla (M)

Endocrinology and Nutrition Department, Parc Taulí University Hospital, Institut d'Investigació i Innovació Parc Taulí (I3PT), Medicine Department, Universitat Autònoma de Barcelona, Parc Taulí 1, 08208, Sabadell, Barcelona, Spain.

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Novel germline variants of CDKN1B and CDKN2C...
Recherchemedicale.com › Phénomènes génétiques › Variation génétique › Mutation › Mutation germinale › Novel germline variants of CDKN1B and CDKN2C...
Recherchemedicale.com › Maladies endocriniennes › Maladies de la parathyroïde › Hyperparathyroïdie › Hyperparathyroïdie primitive › Novel germline variants of CDKN1B and CDKN2C...
Recherchemedicale.com › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › Novel germline variants of CDKN1B and CDKN2C...
Recherchemedicale.com › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › Novel germline variants of CDKN1B and CDKN2C...
Recherchemedicale.com › Cellules › Cellules germinales › Novel germline variants of CDKN1B and CDKN2C...
Recherchemedicale.com › Tumeurs › Novel germline variants of CDKN1B and CDKN2C...
Recherchemedicale.com › Maladies endocriniennes › Tumeurs des glandes endocrines › Néoplasie endocrinienne multiple › Néoplasie endocrinienne multiple de type 1 › Novel germline variants of CDKN1B and CDKN2C...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Protéines inhibitrices des kinases cyclines-dépendantes › Inhibiteur p27 de kinase cycline-dépendante › Novel germline variants of CDKN1B and CDKN2C...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Protéines inhibitrices des kinases cyclines-dépendantes › Inhibiteur p18 de kinase cycline-dépendante › Novel germline variants of CDKN1B and CDKN2C...