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BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Fluoruracila/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Neoplasias do Colo/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Neoplasias Retais/tratamento farmacológicoRESUMO
OBJECTIVE: The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes. METHODS: The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response. RESULTS: Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16). CONCLUSION: Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates.
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Neoplasias , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/patologia , Turquia , Adulto , Idoso , Sequenciamento de Nucleotídeos em Larga Escala , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética , Medicina de Precisão , Resultado do Tratamento , Relevância ClínicaRESUMO
SLC35D1 gene encodes UDP-glucuronic acid/UDP-n-acetylgalactosamine dual transporter protein and transports organic or inorganic molecules across cellular membranes. SLC35D1 gene pathogenic variants causes Schneckenbecken dysplasia (SHNKND) which is a rare lethal autosomal recessive disorder characterized by the snail-like pelvis, flattening of vertebral bodies, short and broad long bones with a dumbbell-like appearance, thoracic hypoplasia. Only six cases with homozygous SLC35D1 variants have been reported to date, and all of these cases were lost in the perinatal period. Here we report different family members with a novel SLC35D1 variant who presented a milder phenotype of SHNKND. The affected patients have common clinical features such as short stature, mild mesomelia, shortening of the lower extremity, genu valgum, and narrow thorax. Exome sequencing of the proband revealed a homozygous missense variant of SLC35D1 gene, c.401 T > C (p. Met134Thr). The affected siblings, their two cousins, and their paternal uncle with a similar phenotype were also homozygous for the variant. This is the first case report of a family with a novel likely pathogenic variant (p. Met134Thr) and mild phenotypic features. It has the largest family with different ages of patients (ages ranged 4-31 years old) reported to date. The present report supports the evidence that the p. Met134Thr variant is responsible for a milder phenotype than previously reported cases with SLC35D1 pathogenic variants.
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Osteocondrodisplasias , Feminino , Humanos , Proteínas de Transporte de Monossacarídeos/genética , Osteocondrodisplasias/genética , Linhagem , Fenótipo , Gravidez , Difosfato de UridinaRESUMO
Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to â¼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1-/- mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy.
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Epilepsia/genética , Glutamato Descarboxilase/genética , Hipotonia Muscular/genética , Transtornos do Neurodesenvolvimento/genética , Anormalidades Múltiplas/genética , Idade de Início , Alelos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , MutaçãoRESUMO
While current neoadjuvant protocols have proven benefits on local control for majority of patients with locally advanced rectal cancer, there are certain clinical conditions that require future advances for improving the outcomes. Total neoadjuvant therapy incorporates systemic chemotherapy planned within standard neoadjuvant protocols either before or after radiotherapy for locally advanced rectal cancer as a whole. Enhanced compliance with planned oncological therapy, tumour downstaging, administration of chemotherapy at the earliest time in the disease course to help assessing chemosensitivity are the proposed benefits of total neoadjuvant therapy in patients with locally advanced rectal cancer. Patient selection criteria for administration of total neoadjuvant therapy in the recent guidelines are unclear. Since current literature is inconclusive for the optimal sequence and type of radiotherapy and chemotherapy, premature incorporation of total neoadjuvant therapy for all locally advanced rectal cancers may result in overtreatment and subsequently toxicity. This article aims to discuss the current literature and to propose a future perspective by considering real-life scenarios reflecting patients' needs for treatment of locally advanced rectal cancer.
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Terapia Neoadjuvante , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia , Humanos , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Reto/patologia , Resultado do TratamentoRESUMO
MicroRNAs (miRNAs) have major roles in nearly all cellular process including gene expression, and may behave as oncogene or tumor suppressor gene by binding to complementary sequences in the target mRNA. The circulating microRNA-15a (miRNA-15a) and microRNA-16-1 (miRNA-16-1) of 15 healthy adults and of 40 untreated patients diagnosed with diffuse large B-cell lymphoma (DLBC) were recruited to investigate the expression levels. The expression levels of miRNA-15a, and miRNA-16-1 genes of the untreated DLBCL patients, and healthy individuals with matched age, sex and ethnicity were examined. MicroRNA expression profiles obtained from peripheral blood were investigated. The samples were collected from 40 patients diagnosed with DLBC patients, and from 15 healthy controls. Two miRNAs were selected, and expression profile was examined using a quantitative real-time polymerase chain reaction (qPCR) based on the previous studies. Statistically significant expression level differences (p < 0.05) were detected for miRNA-16-1 in DLBCL patients and healthy control groups. miRNA-16-1 gene expression level was found approximately ninefold higher in the patient group compared to the controls; however, no statistical difference was detected in the expression profile of miRNA-15a between the both groups. On the other hand, the decreased gene expression in miRNA16-1 was observed in 88.3% of DLBCL patients. These results suggested that there was no statistically significant decrease in the miRNA-15a gene expression in DLBCL patients (p > 0.05). On the contrary to the literature, miRNA-16-1 expression level was suppressed in DLBCL group in our study, however no whole gene silencing was performed. MicroRNA-16-1 might be suggested to behave as a tumor suppressor in DLBCL in our study.
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Regulação Neoplásica da Expressão Gênica , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , MicroRNAs/genética , Células Neoplásicas Circulantes/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-IdadeAssuntos
Neoplasias do Apêndice , Tumores Neuroendócrinos , Humanos , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Neoplasias do Apêndice/cirurgia , Neoplasias do Apêndice/patologia , Colectomia/efeitos adversos , Pacientes , Apendicectomia/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: Triple negative breast cancer (TNBC) is characterized by high rates of recurrence, especially in patients with residual disease after neoadjuvant chemotherapy (NAC). Capecitabine is being used as standard adjuvant treatment in residual TNBC. We aimed to investigate the real-life data regarding the efficacy of capecitabine in residual TNBC. DESIGN AND METHODS: In this retrospective multicenter study, TNBC patients with residual disease were evaluated. Patients, who received standard anthracycline and taxane-based NAC and adjuvant capecitabine were eligible. Overall survival (OS), disease free survival (DFS) and toxicity were analyzed. RESULTS: 170 TNBC patients with residual disease were included. Of these, 62.9% were premenopausal. At the time of analysis, the recurrence rate was 30% and death rate was 18%. The 3-year DFS and OS were 66% and 74%, respectively. In patients treated with adjuvant capecitabine, residual node positive disease stood out as an independent predictor of DFS (p = 0.024) and OS (p = 0.032). Undergoing mastectomy and the presence of T2 residual tumor was independent predictors of DFS (p = 0.016) and OS (p = 0.006), respectively. CONCLUSION: The efficacy of capecitabine was found lower compared to previous studies. Selected patients may have further benefit from addition of capecitabine. The toxicity associated with capecitabine was found lower than anticipated.
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Antimetabólitos Antineoplásicos , Capecitabina , Neoplasias de Mama Triplo Negativas , Humanos , Capecitabina/uso terapêutico , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Quimioterapia Adjuvante/métodos , Antimetabólitos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/administração & dosagem , Intervalo Livre de Doença , Turquia , Idoso , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasia Residual , Taxa de Sobrevida , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , MastectomiaRESUMO
BACKGROUND: Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy. The tumor-agnostic nature of MSI makes it a denominator for immunotherapy in several solid tumors. It can be assessed using next-generation sequencing (NGS), fluorescent multiplex PCR, and immunohistochemistry (IHC). CASE SUMMARY: Here, we report 3 cases with discordant MSI results detected using different methods. A cholangiocellular carcinoma case revealed proficient mismatch repair (MMR) by IHC but high MSI (MSI-H) by liquid NGS. A cervical cancer case revealed deficient MMR by IHC, microsatellite stable by PCR, and MSI-H by NGS. Lastly, an endometrial cancer case revealed proficient MMR by IHC but MSI-H by NGS. CONCLUSION: IHC for MMR status is the first choice due to several advantages. However, in cases of indeterminate IHC results, molecular testing by MSI-PCR is preferred. Recently, NGS-based MSI assays are being widely used to detect MSI-H tumors. All three methods have high accuracy; however, the inconsistencies between them may lead to misdiagnosis.
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In the last few decades, the treatment strategy for locally advanced resectable gastric cancer (GC) has shifted to a multimodal approach, which potentially decreases recurrence risk and improves survival rates. Perioperative therapy leads to downstaging, increased curative resection rates, and prolonged disease-free and overall survival, by preventing micrometastases in patients with resectable GC. Application of neoadjuvant therapy provides information about tumor biology and in vivo sensitivity. A consensus regarding the therapeutic approach for non-metastatic GC does not exist, and many clinical trials aim to clarify this aspect. Advances in precision medicine and the role of immunotherapy have been the focus of research in GC treatment. Herein, the current status and possible future developments of perioperative therapy for locally advanced resectable GC are reviewed, based on the most recent randomized clinical trials.
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Background: Mismatch repair (MMR) deficiency is a fundamental factor affecting the management treatment outcomes of colorectal cancer (CRC). MMR status can be diagnosed by both immunohistochemistry (IHC) polymerase chain reaction (PCR). Since tumors with MMR deficiency are prone to respond to immunotherapy immune checkpoint inhibitors are used to treat such tumors. Case presentation: A 69-year-old male patient presented to an outside clinic with weight loss and abdominal pain. Radiological investigations detected a mesenteric mass of 10 cm, peritoneal implants, and mediastinal lymphadenopathy. The eventual biopsy result from the mesenteric mass was mucinous adenocarcinoma with a goblet cell pattern. Since the IHC result was unclear for deficiency in mismatch repair (dMMR) metastatic CRC (mCRC), the diagnosis was confirmed with PCR. The patient received 8 cycles of FOLFIRINOX + bevacizumab followed by FOLFOX combined with pembrolizumab. No adverse effect was reported related to immunotherapy which resulted in radiologic and metabolic regression. The patient underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). The final pathology results revealed a pathological complete response and R0 resection. In the 6th month follow-up, no recurrence or metastasis was reported. Conclusion: Chemotherapy and immunotherapy combination is a promising treatment modality which can also be used for mCRC. This is the index case who received chemotherapy in combination with immunotherapy for mucinous adenocarcinoma of the colon with a goblet cell pattern and had pCR.
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Tumor Carcinoide , Neoplasias do Colo , Humanos , Masculino , Idoso , Tumor Carcinoide/terapia , Dor Abdominal/etiologia , Neoplasias do Colo/terapia , Protocolos de Quimioterapia Combinada Antineoplásica , Imunoterapia , Repetições de Microssatélites , Instabilidade de Microssatélites , Redução de PesoRESUMO
Here, we report a new case with chromosome 22q11 deletion and cardiac anomaly diagnosed prenatally by echocardiography. Fluorescence in situ hybridization (FISH) analysis demonstrated a heterozygous deletion at 22q11.2. Echocardiography revealed ventricular septal defect, pulmonary atresia, and aneurysm of the main pulmonary artery and its branches. Pulmonary artery aneurysm (PAA) is rarely seen in patients with 22q11.2 deletion syndrome (22qDS). In this case, PAA was found by prenatal echocardiographic examination at the 25th week of gestation. To date, no prenatally diagnosed case of 22qDS with PAA has been reported. This is the first 22qDS case with PAA that was detected prenatally by FISH analysis.
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Aneurisma/diagnóstico , Deleção Cromossômica , Síndrome de DiGeorge/genética , Artéria Pulmonar/anormalidades , Aneurisma/genética , Cromossomos Humanos Par 22 , Síndrome de DiGeorge/diagnóstico , Feminino , Comunicação Interventricular/diagnóstico , Comunicação Interventricular/genética , Humanos , Hibridização in Situ Fluorescente , Gravidez , Atresia Pulmonar/diagnóstico , Atresia Pulmonar/genética , Ultrassonografia Pré-Natal , Adulto JovemRESUMO
Uncertainties and risks play a central role in creating vulnerabilities for logistics service operations. Over the years, Logistic Service Providers (LSPs) have learned how to ensure resilience to confront uncertainties and risks triggered by adverse events. However, quite unlike any seen in recent times, the COVID-19 pandemic brings about unavoidable uncertainties and risks for the logistics industry. Yet, there is no common approach to contextualize how they interact together. We incorporate an empirical research design and make a threefold contribution: first, we identify uncertainties and risks that LSPs encounter during the COVID-19 pandemic and investigate their prominence. Second, we unveil intertwined schemes of afore-identified uncertainties and risks and augment the understanding of their cause-effect structure. Third, we provide an uncertainty and risk assessment guideline for LSPs affected by threats emerging from unforeseeable crises. In this study, we combine qualitative work and the fuzzy DEMATEL method. Qualitative thematic analysis of in-depth interviews reveals the most important uncertainties (COVID-19 measures, employee welfare, forecast horizon, demand change, and government regulations) and risks (COVID-19 risk, delivery delays, supply chain disruptions, financial failure, and product returns) for LSPs. The fuzzy DEMATEL method shows that COVID-19 measures and COVID-19 risk are highly prominent and influence other factors. The results indicate that demand change, government regulations, and supply chain disruptions are net causers, and employee welfare, financial failure, forecast horizon, delivery delays, and product returns are net receivers. Distinctly, employee welfare is the most affected factor, empirically confirming that major risks for LSPs are related to the human factor. More investigation in our results suggests that supply chain disruptions and demand change, two factors triggered by the COVID-19 pandemic, influence financial failure and forecast horizon, two factors associated with operational performance.
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Background: Complex chromosome rearrangements (CCRs) involve more than 2 chromosomal breakpoints and cause the exchanges of chromosomal segments between two or more chromosomes. The carriers of CCRs have normal phenotypes, but they have a higher risk of reproductive failure. Case Presentation: This paper presents a couple with a history of two affected children, one spontaneous abortion, three in vitro fertilization (IVF) failures, and one healthy boy who were referred to our laboratory for preimplantation genetic testing (PGT). The wife had been evaluated as a carrier of 46,XX,t (2;6)(p21;p25); therefore, four IVF treatment cycles supported with PGT for this translocation had been performed in different IVF centers until the couple consulted our laboratory. Only one of these four IVF attempts had resulted in a healthy boy and this IVF study had been performed with fluorescence in situ hybridization (FISH)-based preimplantation genetic testing for structural chromosomal rearrangements (PGT-SR). The fifth IVF study with next-generation sequencing (NGS)-based PGT was performed by our laboratory and no healthy embryo was found in evaluated 6 embryos. During our NGS-based PGT, the cryptic involvement of 12p was firstly detected. FISH with chromosome 2,6, and 12 specific probes revealed that the mother was a carrier of a balanced 3-way translocation of 46,XX,t(2;6;12)(p21;p25;p13). Conclusion: NGS based PGT-SR method is an accurate method for detecting the copy number variations and is helpful to find out the cryptic CCRs.
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Background: Extramural venous invasion is an independent predictor of poor outcome in colorectal cancer, whereas the significance of the intramural component of venous and lymphatic and perineural invasion is unclear. Aims: To evaluate the prognostic impact of intramural components for venous, lymphatic, and perineural invasions and the relation of these invasion patterns with clinicopathological features in patients with colon cancer. Study Design: A retrospective cross-sectional study. Methods: The analysis included 626 patients with colon cancer in stages II and III. All patients were divided into four categories (no invasion, intramural invasion only, extramural invasion only, or both intramural and extramural invasions) for vascular invasion, lymphatic invasion and perineural invasion. The primary outcomes were 5-year disease-free and overall survival. Results: Right-sided (for vascular invasion, 24.7% vs. 33.9%, p = 0.007; for perineural invasion, 34.5% vs. 41.5%, p = 0.034) and dMMR tumors (for vascular invasion, 13.5% vs. 33.5, p < 0.001; for perineural invasion, 25% vs. 41.4%, p = 0.004) exhibited less venous and perineural invasion. Compared with no invasion, presence of intramural invasion only, did not exert any effect on disease-free or overall survival for vascular invasion, lymphatic invasion, and perineural invasion. Multivariate analyses revealed that the presence of both intramural and extramural invasion was independently associated with poor disease-free and overall survival for venous (hazard ratios: 2.39, p = 0.001; hazard ratios: 2.46, p = 0.001), lymphatic (hazard ratios: 2.456, p < 0.001; hazard ratios: 2.13, p = 0.02) and perineural invasion (hazard ratios: 2.99, p < 0.001; hazard ratios: 2.68, p < 0.001), respectively. Conclusion: Our data strongly advocates the importance of reporting intramural and extramural components of invasion since the presence of intramural invasion alone may not be considered as a high-risk factor for systemic recurrence.
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Neoplasias do Colo , Humanos , Neoplasias do Colo/patologia , Estudos Transversais , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
Colorectal cancer is the third most common cancer in Turkey. The current guidelines do not provide sufficient information to cover all aspects of the management of rectal cancer. Although treatment has been standardized in terms of the basic principles of neoadjuvant, surgical, and adjuvant therapy, uncertainties in the management of rectal cancer may lead to significant differences in clinical practice. In order to clarify these uncertainties, a consensus program was constructed with the participation of the physicians from the Acibadem Mehmet Ali Aydinlar and Koç Universities. This program included the physicians from the departments of general surgery, gastroenterology, pathology, radiology, nuclear medicine, medical oncology, radiation oncology, and medical genetics. The gray zones in the management of rectal cancer were determined by reviewing the evidence-based data and current guidelines before the meeting. Topics to be discussed consisted of diagnosis, staging, surgical treatment for the primary disease, use of neoadjuvant and adjuvant treatment, management of recurrent disease, screening, follow-up, and genetic counseling. All those topics were discussed under supervision of a presenter and a chair with active participation of related physicians. The consensus text was structured by centralizing the decisions based on the existing data.
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Neoplasias Retais , Terapia Combinada , Consenso , Humanos , Oncologia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Neoplasias Retais/terapiaRESUMO
Chromosome fragile sites tend to form gap or break in chromosomes when the cells are exposed to replication stress. Folic acid deprivation in the culture medium induces folate-sensitive rare fragile sites, such as FRAXA which is responsible for the fragile X mental retardation syndrome. Chromosome instability at fragile sites can be evaluated by biomarkers of genomic instability such as frequency of micronuclei (MN). It was aimed to analyse the chromosome content of MN in Fragile X cells during folate deprivation by the MN-fluorescence in situ hybridization (FISH) method. Samples from five Fragile X syndrome patients, diagnosed using cytogenetic and molecular methods, as well as from their parents and five controls were included in the study. Blood samples were cultured in two different culture media (folate-deficient and normal). Results of MN-FISH test were analysed in terms of MN frequency and chromosome content of MN. An accumulation of MN in Fragile X patients, mainly containing T (+) or C (+) MN or T (+) plus C (+) MN in binucleated cells was found. Finally, MN-FISH analysis allowed confirming that the increase in MN frequency is due to a higher sensitivity to chromosome breakage along the X chromosome.
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In this report, detailed clinical features of a female patient and a new mutation that was not previously identified in the WD repeat-containing protein 45 (WDR45) gene are presented in order to contribute to the information in the literature on the phenotype as well as genotype of Beta-Propeller Protein Associated Neurodegeneration. Whole Exome Sequencing (WES) analysis was done since etiology could not be determined. Our case was admitted to the hospital due to epilepsy, growth retardation and autism. Her family history was unremarkable except consanguineous marriage. She had tonic seizures twice at the age of 7 and 12 months and had continual seizures after 16 months. At the time, electroencephalography and brain MRI were performed twice were determined to be normal. Brain MRI Spectroscopy was also found to be normal at 35 months of age. Metabolic screening tests (acyl carnitine profile, urine organic acids, plasma amino acids, a very long chain fatty acid profile, etc.) were also normal. Genetic screening of the epilepsy panel for epileptic encephalopathies was negative. WES analysis revealed heterozygous previously unreported variant in intron 6 of the WDR45 gene, c.344+5G > A. In conclusion; Beta-Propeller Protein Associated Neurodegeneration should be considered as an option in the diagnosis of female patients with clinical findings of epilepsy, growth retardation and autism, with unspecified etiology.
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Proteínas de Transporte , Epilepsia , Proteínas de Transporte/genética , Eletroencefalografia , Epilepsia/genética , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , MutaçãoRESUMO
In this report, detailed clinical features of a female patient and a new mutation that was not previously identified in the WD repeat-containing protein 45 (WDR45) gene are presented in order to contribute to the information in the literature on the phenotype as well as genotype of Beta-Propeller Protein Associated Neurodegeneration. Whole Exome Sequencing (WES) analysis was done since etiology could not be determined. Our case was admitted to the hospital due to epilepsy, growth retardation and autism. Her family history was unremarkable except consanguineous marriage. She had tonic seizures twice at the age of 7 and 12 months and had continual seizures after 16 months. At the time, electroencephalography and brain MRI were performed twice were determined to be normal. Brain MRI Spectroscopy was also found to be normal at 35 months of age. Metabolic screening tests (acyl carnitine profile, urine organic acids, plasma amino acids, a very long chain fatty acid profile, etc.) were also normal. Genetic screening of the epilepsy panel for epileptic encephalopathies was negative. WES analysis revealed heterozygous previously unreported variant in intron 6 of the WDR45 gene, c.344+5G > A. In conclusion; Beta-Propeller Protein Associated Neurodegeneration should be considered as an option in the diagnosis of female patients with clinical findings of epilepsy, growth retardation and autism, with unspecified etiology.