1. Alazami syndrome: the first case of papillary thyroid carcinoma
- Author
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Simonetta Rosato, Andrea Frasoldati, Elisa Magnani, Livia Garavelli, Leslie Matalonga, Ivan Ivanovski, Sergio Bernasconi, Orsetta Zuffardi, Chiara Baldo, Davide Nicoli, Stefano Giuseppe Caraffi, Simonetta Piana, and Marzia Pollazzon more...
- Subjects
Male ,Proto-Oncogene Proteins B-raf ,0301 basic medicine ,Oncology ,Heterozygote ,medicine.medical_specialty ,Developmental Disabilities ,Dwarfism ,030105 genetics & heredity ,Gene mutation ,Thyroid carcinoma ,Young Adult ,03 medical and health sciences ,Thyroid peroxidase ,Intellectual Disability ,Internal medicine ,Exome Sequencing ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Thyroid Neoplasms ,Global developmental delay ,Hypertelorism ,Frameshift Mutation ,Thyroid cancer ,Genetics (clinical) ,Exome sequencing ,biology ,business.industry ,Cancer ,medicine.disease ,Phenotype ,030104 developmental biology ,Italy ,Ribonucleoproteins ,Thyroid Cancer, Papillary ,biology.protein ,medicine.symptom ,business - Abstract
Alazami syndrome (MIM#615071) is a rare developmental disorder caused by biallelic variants in the LARP7 gene. Hallmark features include short stature, global developmental delay, and distinctive facial features. To date, 23 patients from 11 families have been reported in the literature. Here we describe a 19-year-old man who, in association with the typical features of Alazami syndrome, was diagnosed at the age of 14 years with papillary thyroid carcinoma, harboring the somatic BRAF V600E mutation. Whole exome sequencing revealed two novel LARP7 variants in compound heterozygosity, whereas only common variants were detected in genes associated with familial nonmedullary thyroid cancer (MIM#188550). LARP7 acts as a tumor suppressor in breast and gastric cancer, and possibly, according to recent studies, in thyroid tumors. Since thyroid cancer is rare among children and adolescents, we hypothesize that the LARP7 variants identified in our patient are responsible for both Alazami syndrome and tumor susceptibility. We also provide an overview of the clinical findings in all Alazami syndrome patients reported to date and discuss the possible pathogenetic mechanism that may underlie this condition, including the role of LARP7 in tumor susceptibility. more...
- Published
- 2019
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