title: A novel in-frame deletion in MEN1 (p.Ala416del) causes familial multiple endocrine neoplasia type 1 with an aggressive phenotype and unexpected inheritance pattern.
abstract: The present study describes a family with multiple endocrine neoplasia type 1 (MEN1) caused by a previously undescribed in-frame deletion c.1246_1248delGCC (Ala416del) in the MEN1 gene. Evidence for the pathogenic character of this mutation, which triggers an aggressive clinical outcome, is demonstrated. Aggregation analysis in the tested family was strongly suggestive of causality of the detected mutation. This was supported by the analysis of LOH (loss of heterozygosity) in tumor-derived DNA and by computational analysis of the functional and structural implications of the mutation. Different phenotypic characteristics were identified among family members, which is typical for MEN1. Additionally, an unexpected disease inheritance pattern was observed in this kindred, in which either all or none of the siblings of one branch inherited the disease.
authors.affiliation: Department of Endocrinology, Jagiellonian University Medical College, 31‑501 Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Skalniak
authors.affiliation: Endocrinology Clinic, University Hospital, 31‑501 Krakow, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Sokołowski
authors.affiliation: Department of Endocrinology, Jagiellonian University Medical College, 31‑501 Krakow, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Jabrocka-Hybel
authors.affiliation: Department of Endocrinology, Jagiellonian University Medical College, 31‑501 Krakow, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Piątkowski
authors.affiliation: Department of Pathomorphology, Jagiellonian University Medical College, 31‑501 Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Białas
authors.affiliation: Department of Endocrinology, Jagiellonian University Medical College, 31‑501 Krakow, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gilis-Januszewska
authors.affiliation: Department of Endocrinology, Jagiellonian University Medical College, 31‑501 Krakow, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Pach
authors.affiliation: Department of Endocrinology, Jagiellonian University Medical College, 31‑501 Krakow, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Hubalewska-Dydejczyk
mesh_terms: D000328:Adult; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns; D019656:Loss of Heterozygosity; D008297:Male; D008958:Models, Molecular; D018761:Multiple Endocrine Neoplasia Type 1 / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D010375:Pedigree; D010641:Phenotype; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D016364:Reading Frames; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins