Diaphanospondylodysostosis: Full Case Report with Novel Pathogenic BMPER Mutation

Diaphanospondylodysostosis is an extremely rare, recessively inherited, perinatal lethal skeletal disorder associated with BMPER gene mutations. Clinically it is characterized by defects in costovertebral ossification, absent ribs, hypertelorism, short nose with depressed nasal bridge, low-set ears, and short neck. At the extraosseous level, the most frequent pathologic finding is nephroblastomatosis with multicystic kidneys. We present the case of a child of non-consanguineous parents who died at 2 months of age in our center. Autopsy showed a marked costovertebral ossification defect, perilobar nephrogenic rests and loss of white matter with periventricular leukomalacia. After genetic study, the diagnosis of diaphanospondylodysostosis was confirmed. A previously undescribed germinal mutation in the BMPER gene (c.576 + 2dupT) was found.

RESPONSE TO NEOADYAVANT CHEMOTHERAPY WITH PLATINUM-BASED DRUGS IN BREAST CANCER PATIENTS WITH BRCA1 DELETION IN TUMOR

Currently, the presence of the germinal mutation BRCA1 5382insC in breast cancer patients is one of the determining factors for prescribing platinum-based drugs. However, this type of mutation is found in no more than 10 % of patients, thus limiting the feasibility of administering platinum-based drugs. Various somatic changes in the BRCA1 gene in breast tumors, in particular the deletions of this gene, can play an important role in the tumor sensitivity to platinum drugs.Case description. We present the case of a 42-year-old woman diagnosed with breast cancer. The deletion of the BRCA1 gene was detected in the tumor. The patient had a complete response to preoperative chemotherapy according to the CP regimen.Conclusion. The frequency of the germline mutation of the BRCA1 gene does not exceed 10 %, and the deletion frequency of this gene can vary from 30 to 45 %, thus greatly increasing the feasibility of using platinum-based drugs in mutationnegative patients to achieve complete pathologic response and high survival rates.

Genetic predictors of insulin-producing pancreatic tumor

Insulinoma is the most common functioning tumor of the pancreas. Approximately 5% of its cases are associated with the multiple endocrine neoplasia syndrome type 1 (MEN1), caused by mutation in the MEN1 gene. MEN1 can be manifested by pituitary and parathyroid adenomas, pancreatic neuroendocrine tumors, tumors of the thyroid gland, adrenals, intestine, carcinoids of lungs and other organs. However, in 5–10% of the patients with clinical manifestation of this syndrome, MEN1 mutations cannot be identified. Moreover, the disease can be caused by various abnormalities (mutations, polymorphisms, etc.) in other genes. More than 30 genes, associated with insulin-producing pancreatic tumors, have been described in the literature. With a known germinal mutation, the prognosis and management of patients with insulinoma can be determined by the hereditary disease with which the tumor is associated. The article emphasizes the need to search for new genetic markers that predispose to the development of insulinoma. The necessity of extended genetic testing of patients with insulinomas is discussed, primarily of young patients with multifocal lesions, family history and associated disorders.