At MedGenome, we are deeply focused on continuous innovation, and publishing our findings for the larger benefit of the genetic testing community. Read through our publications for details of our latest work.
Immunodeficiency, Motor Delay, and Hypouricemia Caused by a Novel Mutation of Purine Nucleoside Phosphorylase Gene in an Indian Infant.
Date: June 1, 2019
We describe an 11-month-old boy who presented with recurrent respiratory infections from 6 months of age. His elder sister died at 10 months with severe septicemia and meningitis. The boy had a mild motor delay. Investigations revealed T cell deficiency and very low serum uric acid suggestive of purine nucleoside phosphorylase (PNP) deficiency – a rare variant of severe combined immunodeficiency disease. A novel homozygous missense mutation of c.597C>G(p. S199R) of exon 5 on PNP gene confirmed the diagnosis. We suggest that uric acid should be a part of investigation profile for unidentified motor delay, as recurrent infections can be late presentation.
Somatic Mutations Profile of a Young Patient With Metastatic Urothelial Carcinoma Reveals Mutations in Genes Involved in Ion Channels
Date: May 29, 2019
“Background: Urothelial carcinoma is the most common malignancy of the bladder and is primarily considered as a disease of the elderly. Studies that address bladder tumor occurrence in young age groups are rare. Case Presentation: A 19-year-old male presented with a gross total painless hematuria. A histology after biopsy revealed a high-grade transitional cell carcinoma with lymph node metastasis. The patient succumbed to the disease on day 72 of the treatment. Here, we used whole-exome sequencing of a paired tumor-normal sample to identify the somatic mutations and the possible targets of treatment. Result: We predicted eight potential driver mutations (TP53 p.V157L, RB1 c.1498+1G>T, MED23 p.L1127P, CTNND1 p.S713C, NSD1 p.P2212A, MED17 p.G556V, DPYD p.Q814K, and SPEN p.S1078*). In addition, we predicted deleterious mutations in genes involved in the ion channels (CACNA1S p.E1581K, CACNG1 p.P71T, CACNG8 p.G404W, GRIN2B p.A1096T, KCNC1 p.G16V, KCNH4 p.E874K, KCNK9 p.R131S, P2RX7 p.A296D, and SCN8A p.R558H). Conclusions: Most likely, mutations in genes involved in ion channels may be responsible for the aggressive behavior of a tumor. Ion channels are the second largest class of drug targets, and may thus serve as a putative potential therapeutic target in advanced stage urothelial carcinoma.”””
Date: May 15, 2019
Diabetes Mellitus (DM) is one among the supreme metabolic issues observed in history since 3000 BCE and has gained much interest recently due to the increasing number of diabetic cases every year. Glucose is considered as the most iconic biomarker for diabetes detection, and fluctuations in its levels are related to different stages of DM. However, methylglyoxal (MG) is evolving as a diabetes marker since it plays a significant role in biological processes Apart from DM, MG causes several metabolic irregularities like hypertension, neuropathy, nephropathy, oxidative stress. Besides, MG is a predominant precursor of advanced glycation end products (AGEs), which result in protein dysfunction, glycation of vascular tissues and aging. In this background, detection of MG has much importance, and the design of smart models is desirable. MG formation, detoxification, and its glycation effects have paved the way for the development of detection strategies which are described in detail here. The direct and indirect methods of MG measurement have been established in the past. At present, techniques like high-performance liquid chromatography, gas chromatography-mass spectrometry, enzyme-linked immunosorbent assay, capillary electrophoresis, electrochemical biosensors have been used to quantify MG present in the samples. Here, we have tried to correlate the function of MG and detection strategies to explain the major challenges posed towards implementation of easy, efficient and accurate standardization.
Whole Genome Sequencing and Comparative Genomic Analysis Reveal Allelic Variations Unique to a Purple Colored Rice Landrace (Oryza sativa ssp. indica cv. Purpleputtu).
Date: May 7, 2019
Purpleputtu (Oryza sativa ssp. indica cv. Purpleputtu) is a unique rice landrace from southern India that exhibits predominantly purple color. This study reports the underlying genetic complexity of the trait, associated domestication and de-domestication processes during its coevolution with present day cultivars. Along-with genome level allelic variations in the entire gene repertoire associated with the purple, red coloration of grain and other plant parts. Comparative genomic analysis using ‘a panel of 108 rice lines’ revealed a total of 3,200,951 variants including 67,774 unique variations in Purpleputtu (PP) genome. Multiple sequence alignment uncovered a 14 bp deletion in Rc (Red colored, a transcription factor of bHLH class) locus of PP, a key regulatory gene of anthocyanin biosynthetic pathway. Interestingly, this deletion in Rc gene is a characteristic feature of the present-day white pericarped rice cultivars. Phylogenetic analysis of Rc locus revealed a distinct clade showing proximity to the progenitor species Oryza rufipogon and O. nivara. In addition, PP genome exhibits a well conserved 4.5 Mbp region on chromosome 5 that harbors several loci associated with domestication of rice. Further, PP showed 1,387 unique when SNPs compared to 3,023 lines of rice (SNP-Seek database). The results indicate that PP genome is rich in allelic diversity and can serve as an excellent resource for rice breeding for a variety of agronomically important traits such as disease resistance, enhanced nutritional values, stress tolerance, and protection from harmful UV-B rays.
Simultaneous diagnosis of unilateral retinoblastoma and contralateral optic pathway glioma in a child with neurofibromatosis type 1
Date: April 9, 2019
First International Conference on RASopathies and Neurofibromatoses in Asia: Identification and advances of new therapeutics.
Date: March 25, 2019
The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis, are a group of syndromes characterized by tumor growth in the nervous system. The RASopathies are a group of syndromes caused by germline mutations in genes that encode components of the RAS/mitogen‐activated protein kinase (MAPK) pathway. The RASopathies include NF1, Noonan syndrome, Noonan syndrome with multiple lentigines, Costello syndrome, cardio‐facio‐cutaneous syndrome, Legius syndrome, capillary malformation arterio‐venous malformation syndrome, and SYNGAP1 autism. Due to their common underlying pathogenetic etiology, all these syndromes have significant phenotypic overlap of which one common feature include a predisposition to tumors, which may be benign or malignant. Together as a group, they represent one of the most common multiple congenital anomaly syndromes estimating to affect approximately one in 1000 individuals worldwide. The subcontinent of India represents one of the largest populations in the world, yet remains underserved from an aspect of clinical genetics services. In an effort to bridge this gap, the First International Conference on RASopathies and Neurofibromatoses in Asia: Identification and Advances of New Therapeutics was held in Kochi, Kerala, India. These proceedings chronicle this timely and topical international symposium directed at discussing the best practices and therapies for individuals with neurofibromatoses and RASopathies.
Adult-Onset Myoclonus-Dystonia Syndrome preceding Characteristic Facial Myoclonus in Indian ADCY5-related Dyskinesia
Date: February 5, 2019
A 21year-old man presented with involuntary jerky movements of his hands and head since age 13. Initially mild, they had progressed to moderate severity over the last few years. The movements could come in ‘spells’ intermittently in the early years. His whole body could tremble when he was anxious, concentrating on an activity or riding his scooter. While he could still do all activities unhindered, and symptoms were mostly an inconvenience, they were increasingly causing embarrassment. Family history was negative. He had never used alcohol. On examination, myoclonic jerking of the neck and both hands was present at rest This article is protected by copyright. All rights reserved. and action. (Video 1, Segment 1) There was no involvement of face, trunk or lower limbs. Brain MRI, metabolic testing, EEG and SSEP were normal. A clinical diagnosis of Myoclonus-Dystonia (M-D) syndrome was made.
A Synthetic DNA, Multi-Neoantigen Vaccine Drives Predominately MHC Class I CD8+ T-cell Responses, Impacting Tumor Challenge.
Date: February 1, 2019
T-cell recognition of cancer neoantigens is important for effective immune-checkpoint blockade therapy, and an increasing interest exists in developing personalized tumor neoantigen vaccines. Previous studies utilizing RNA and long-peptide neoantigen vaccines in preclinical and early-phase clinical studies have shown immune responses predominantly driven by MHC class II CD4+ T cells. Here, we report on a preclinical study utilizing a DNA vaccine platform to target tumor neoantigens. We showed that optimized strings of tumor neoantigens, when delivered by potent electroporation-mediated DNA delivery, were immunogenic and generated predominantly MHC class I-restricted, CD8+ T-cell responses. High MHC class I affinity was associated specifically with immunogenic CD8+ T-cell epitopes. These DNA neoantigen vaccines induced a therapeutic antitumor response in vivo, and neoantigen-specific T cells expanded from immunized mice directly killed tumor cells ex vivo These data illustrate a unique advantage of this DNA platform to drive CD8+ T-cell immunity for neoantigen immunotherapy.
Novel GNAL mutation in an Indian patient with generalized dystonia and response to deep brain stimulation
Date: January 14, 2019
Mutations in GNAL have been associated with cranio-cervical dystonia (DYT-GNAL) [ 1 ]. The dystonia most often progresses to involve other regions, particularly the face and laryngeal muscles and less commonly the trunk, arm and lower limbs. The clinical phenotype in GNAL-related dystonia appears to be similar to that caused by mutations in THAP1
Differential methylation of the type 2 diabetes susceptibility locus KCNQ1 is associated with insulin sensitivity and is predicted by CpG site specific genetic variation.
Date: January 11, 2019
Epigenetic mechanisms regulate gene expression and may influence the pathogenesis of type 2 diabetes through the loss of insulin sensitivity. The aims of this study were to measure variation in DNA methylation at the type 2 diabetes locus KCNQ1 and assess its relationship with metabolic measures and with genotype.