Rhabdoid tumor predisposition syndrome caused by SMARCB1 constitutional deletion: prenatal detection of new case of recurrence in siblings due to gonadal mosaicism.
Rhabdoid tumors are aggressive malignancies that show loss-of-function mutations of SMARCB1 gene, a member of the SWI/SNF chromatin-remodeling complex controlling gene transcription. One-third of patients affected by rhabdoid tumor harbor a germ-line mutation of SMARCB1 defining a rhabdoid tumor predisposition syndrome. The occurrence of a second somatic mutation determines the development of neoplasia in a two-hit model. Most germ-line mutations occur de novo, and few cases of recurrence in a sibship have been described. Here we report on a new Italian family with recurrence of SMARCB1 germ-line deletion in two siblings due to gonadal mosaicism. The deletion was identified in the 9-month-old proband with malignant rhabdoid tumor of the right kidney and disseminated metastases. Testing of both parents confirmed the de novo origin of the mutation, but recurrence was then detected prenatally in a new pregnancy. This is the sixth family with malignant rhabdoid tumor predisposition syndrome with the recurrence of the same germ-line SMARCB1 mutation in the sibship but not in healthy parents, suggesting that gonadal mosaicism is a less rare event than supposed. The clinical outcome in our patient confirms previous data of poorer outcome in patients with rhabdoid tumor predisposition syndrome.
Genetics Section, Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Via Montpellier 1, 00197, Rome, Italy. laura.gigante84@gmail.com.
Laura
http://orcid.org/0000-0002-9327-3475
L
Gigante
Department of Biomedical Experimental and Clinical Sciences, Medical Genetics, University of Florence, Florence, Italy.
Irene
I
Paganini
CNR Institute of Translational Pharmacology, Rome, Italy.
Marina
M
Frontali
Department of Biomedical Experimental and Clinical Sciences, Medical Genetics, University of Florence, Florence, Italy.
Serena
S
Ciabattoni
Genetics Section, Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Via Montpellier 1, 00197, Rome, Italy.
Federica Carla
FC
Sangiuolo
Department of Biomedical Experimental and Clinical Sciences, Medical Genetics, University of Florence, Florence, Italy.
Laura
L
Papi
D001932:Brain Neoplasms / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D009030:Mosaicism; D060885:Multiplex Polymerase Chain Reaction; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D018335:Rhabdoid Tumor / Q000235:genetics*; D000071796:SMARCB1 Protein; D035781:Siblings; D014157:Transcription Factors / Q000235:genetics*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors
22q deletion; Gonadal mosaicism; Prenatal diagnosis; Rhabdoid tumor; SMARCB1