Chromosomal translocation disrupting the SMAD4 gene resulting in the combined phenotype of Juvenile polyposis syndrome and Hereditary Hemorrhagic Telangiectasia

Autor: Lilian Bomme Ousager, Anette Drøhse Kjeldsen, Katrine S. Aagaard, Martin Jakob Larsen, Klaus Brusgaard, Emilie B. Lester, Pernille Mathiesen Tørring, Ieva Miceikaite
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Adult
Male
congenital
hereditary
and neonatal diseases and abnormalities
lcsh:QH426-470
gastrointestinal cancer
Chromosomal translocation
Locus (genetics)
JP‐HHT
030105 genetics & heredity
Biology
JP-HHT
SMAD4
Germline
Clinical Reports
Translocation
Genetic
HHT
chromosomal translocation
03 medical and health sciences
Chromosome Breakpoints
Neoplastic Syndromes
Hereditary
Genetics
medicine
otorhinolaryngologic diseases
Humans
Juvenile polyposis syndrome
Molecular Biology
Genetics (clinical)
Hereditary Hemorrhagic Telangiectasia
Smad4 Protein
Clinical Report
Intestinal Polyposis
balanced translocation
Breakpoint
Chromosome
ACVRL1
medicine.disease
Phenotype
Pedigree
JPHT
juvenile polyposis syndrome
lcsh:Genetics
030104 developmental biology
Chromosomes
Human
Pair 1
Female
Telangiectasia
Hereditary Hemorrhagic
Chromosomes
Human
Pair 18
Zdroj: Molecular Genetics & Genomic Medicine, Vol 8, Iss 11, Pp n/a-n/a (2020)
Aagaard, K S, Brusgaard, K, Miceikaite, I, Larsen, M J, Kjeldsen, A D, Lester, E B, Ousager, L B & Tørring, P M 2020, ' Chromosomal translocation disrupting the SMAD4 gene resulting in the combined phenotype of Juvenile polyposis syndrome and Hereditary Hemorrhagic Telangiectasia ', Molecular Genetics and Genomic Medicine, vol. 8, no. 11, e1498 . https://doi.org/10.1002/mgg3.1498
Molecular Genetics & Genomic Medicine
ISSN: 2324-9269
Popis: Background Patients with germline variants in SMAD4 can present symptoms of both juvenile polyposis syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HHT): JP‐HHT syndrome. Next‐Generation Sequencing (NGS) techniques disclose causative sequence variants in around 90% of HHT patients fulfilling the Curaçao criteria. Here we report a translocation event involving SMAD4 resulting in JP‐HHT. Methods A patient fulfilling the Curaçao criteria was analyzed for variants in ENG, ACVRL1, and SMAD4 using standard techniques. Whole‐genome sequencing (WGS) using both short‐read NGS technology and long‐read Oxford Nanopore technology was performed to define the structural variant and exact breakpoints. Results No pathogenic variant was detected in ENG, ACVRL1, or SMAD4 in DNA extracted from blood. Due to abortus habitualis, the proband´s daughter was submitted for chromosomal analysis, and a cytogenetically balanced chromosomal reciprocal translocation t(1;18)(p36.1;q21.1) was detected in the daughter and the patient. The balanced translocation segregated with both gastrointestinal cancer and HHT in the family. WGS provided the exact breakpoints of the reciprocal translocation proving disruption of the SMAD4 gene. Discussion A disease‐causing reciprocal translocation between chromosome 1 and 18 with a breakpoint in the SMAD4 locus co‐segregated with JP‐HHT in an extended family. This observation warrants further analysis for chromosomal rearrangements in individuals with clinical HHT or JP‐HHT of unknown cause.
A disease‐causing balanced reciprocal translocation between chromosome 1 and 18, with a breakpoint in the SMAD4 locus, co‐segregated with JP‐HHT in an extended family.
Databáze: OpenAIRE
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