Novel compound heterozygous variants in XYLT1 gene caused Desbuquois dysplasia type 2 in an aborted fetus: a case report

Background Desbuquois dysplasia type 2 (DBQD2) is an infrequent dysplasia with a wide range of symptoms, including facial deformities, growth retardation and short long bones. It is an autosomal recessive disorder caused by mutations in the XYLT1 gene that encodes xylosyltransferase-1. Case presentation We studied an aborted fetus from Iranian non-consanguineous parents who was therapeutically aborted at 19 weeks of gestation. Ultrasound examinations at 18 weeks of gestation revealed growth retardation in her long bones and some facial problems. Whole-exome sequencing was performed on the aborted fetus which revealed compound heterozygous XYLT1 mutations: c.742G>A; p.(Glu248Lys) and c.1537 C>A; p.(Leu513Met). Sanger sequencing and segregation analysis confirmed the compound heterozygosity of these variants in XYLT1. Conclusion The c.1537 C>A; p.(Leu513Met) variant has not been reported in any databases so far and therefore is novel. This is the third compound heterozygote report in XYLT1 and further supports the high heterogeneity of this disease

Novel in-frame deletion in MFSD8 gene revealed by trio whole exome sequencing in an Iranian affected with neuronal ceroid lipofuscinosis type 7: a case report

Abstract Background The neuronal ceroid lipofuscinoses are a group of neurodegenerative, lysosomal storage disorders. They are inherited as an autosomal recessive pattern with the exception of adult neuronal ceroid lipofuscinosis, which can be inherited in either an autosomal recessive or an autosomal dominant manner. The neuronal ceroid lipofuscinoses are characterized by accumulation of autofluorescent lipopigments in the cells and one of the most important pathological manifestations is ceroid accumulation in the lysosomes. Various types of neuronal ceroid lipofuscinoses are categorized based on the clinical manifestations and the genes involved. Accumulatively, 15 different genes have been found so far to be implicated in the pathogenesis of at least nine different types of neuronal ceroid lipofuscinoses, which result in similar pathological and clinical manifestations. Case presentation A 5-year-old Iranian boy affected by a neurodegenerative disorder with speech problems, lack of concentration, walking disability at age of 4 years leading to quadriplegia, spontaneous laughing, hidden seizure, clumsiness, psychomotor delay, and vision deterioration at age of 5 years, which could be the consequence of macular dystrophy, was referred to us for genetic testing. Trio whole exome sequencing, Sanger validation, and segregation analysis discovered a novel in-frame small deletion c.325_339del (p.Val109_Ile113del) in MFSD8 gene associated with neuronal ceroid lipofuscinosis type 7. Conclusions The deletion found in this patient affects the exon 5 of this gene which is the region encoding transmembrane domain. Sequencing analysis in this family has shown that the index is homozygous for 15 base pairs in-frame deletion, his uncle has normal homozygous, and his parents are heterozygous. This pattern of mutation inheritance and the signs and symptoms observed in the affected male of this family are compatible with what is described in the literature for neuronal ceroid lipofuscinosis type 7 and, therefore, suggest that the MFSD8 gene deletion found in this study is most probably the cause of disease in this family

Pharmacogenetics and Personalized Medicine in Pancreatic Cancer

Pancreatic cancer (PC) is a progressive, fatal disease with a high degree of malignancy. More than 40000 peoplediefrom this cancer annually in the United States. As a multifactorial condition, PC has a complex nature, and there are several genes and signalingpathwaysimplicated in PC pathogenesis and progression. There are diffèrent mutations in master genesincludingtumorsuppressors and oncogenesthat lead to Pancreaticintraepithelialneoplasia (PanIN) whichis the mostcommon non-invasive precursorlesion of pancreatic cancer. These mutations influence directly or indirectly the cycle of Pharmacodynamics profile. Interactions between genetics and drug metabolism could be considered as one of the most important insights in the personalized medicine and targeted therapy based on the genetic profile of each affected person. In this literature, we will discuss pathogenesis and susceptibility to PC, pharmacogenetics and personalized medicine in pancreatic cancer and scrutinized the most important genes, variations and signaling pathways that influence individualized therapy of PC

Horizons of personalized medicine in breast cancer treatment: review article

Breast cancer that is caused by the accumulation of genetic and epigenetic alterations, is one of the main causes of death resulted from cancer. Various therapeutic approaches have been introduced for this cancer and the traditional diagnosis and treatment is based on the prognosis estimation using cancer anatomic features (TNM system) and clinical results, but studies show different responses of these treatments and recurrence after those in some patients. This diversity is resulted by the differences in biological and molecular characteristics. So genomic and molecular studies became more important and the role of targeted treatment based on an individual's genome was highlighted. Today, the progression in personalized medicine using specific individual genome profile has been possible. The ultimate goal of such studies, in the setting of the personalized medicine, is providing markers which can be used to risk assessment of progressing disease. This new science cause great development in the treatment of breast cancer by recognition of specific markers and application of targeted therapy. Trastuzumab and tamoxifen are the most common monoclonal antibodies applied in these patients depends on their biological and molecular profile. The good response to tamoxifen is seen only in patients with estrogen receptor (ER+) which inhibits the binding of estrogen to its receptor. Defect in the metabolizer enzyme of tamoxifen (CYP2D6), which convert it to the active forms, results in the increased risk of recurrence after treatment. Fulvestrant is another monoclonal antibody which its effect is similar to tamoxifen. Trastuzumab suppresses the cell growth by binding inhibition of epidermal growth factor to HER2 receptors. In the metastatic form of disease, the patients may show resistance to trastuzumab, so lapatinib is suitable alternative in these cases. Pertuzumab combination with trastuzumab and chemotherapy with taxane blocks the dimerization of HER2 with another form of HER receptors. The application of personalized medicine in triple negative phenotype is limited due to the lack of appropriate targets and biomarkers, it makes necessary to do further studies. The aim of this review was to describing the different aspects of personalized medicine and introducing the most important biomarkers and targets in the treatment of breast cancer

Case Report of RANBP2 Mutation and Familial Acute Necrotizing Encephalopathy

Introduction. Acute necrotizing encephalopathy (ANE), a rare entity with unique clinical presentation, can be associated significant morbidity and mortality. The majority of ANE reported cases are sporadic. However, reports of extremely rare familial cases are scarce. Case Presentation. We described three cases, two siblings and their cousin, affected by ANE, all of them exhibiting RAN-binding protein 2 (RANBP2) gene mutation. They all presented with seizure and decreased level of consciousness. Unlike the siblings, the cousin eventually expired mainly due to the delay in diagnosis, resulting from late presentation of typical brain involvements of ANE in magnetic resonance imaging (MRI). Conclusion. The presented cases are the first reports of familial ANE in Iran. Attempt was made to raise awareness on this disease, because high clinical suspicion plays an important role in the early diagnosis and proper management of these patients