L.K. Prashanth, Sakthivel Murugan, Vikram Kamath, Ravi Gupta, Rakesh Jadav, S. Sreekantaswamy and Vedam L. Ramprasad (2015). Movement Disorders – Clinical Practice, Vol. 2, Issue 3.
Kufor-Rakeb syndrome (KRS; PARK 9) is a rare autosomal-recessive form of juvenile-onset Parkinson’s disease (PD) caused by ATP13A2 gene mutations. The classical description of KRS is that of rapidly progressive symptoms in the form of parkinsonism, spasticity, supranuclear upgaze paresis, facial-faucial-finger minimyoclonus, visual hallucinations, oculogyric dystonic spasms, and dementia, usually noted between 12 and 16 years of age, resulting in early severe motor handicap. World-wide prevalence of KRS is unknown, with only case reports/series being published.[2, 3] We report on the first case of KRS from India, with previously unreported nonsense mutation in exon 22 ofATP13A2 gene (chr1: 17316187; G>A).
John D. Hulleman, Annie Nguyen, V.L. Ramprasad, Sakthivel Murugan, Ravi Gupta, Avinash Mahindrakar, Ravi Angara, Chandrasekhar Sankurathri, V. Vinod Mootha (2016). Molecular Vision, 22, 73-81.
Retinitis pigmentosa (RP) is the most common inherited form of retinal degeneration, affecting nearly 1/4,000 individuals . RP is caused by progressive rod photoreceptor degeneration ultimately leading to peripheral vision loss, night blindness, and, sometimes, complete blindness. Mutations in more than 50 genes have been identified to cause nonsyndromic RP, while mutations in a smaller subset of genes have been found to cause syndromic RP (i.e., RP combined with additional symptoms in other tissues/organs). Common forms of syndromic RP include Usher syndrome , Refsum disease , and Bardet-Biedl syndrome (BBS) . Of these disorders, BBS is one of the most studied.
Raphael Bueno1,8, Eric W Stawiski2,3,8, Leonard D Goldstein2,3,8, Steffen Durinck2,3,8, Assunta De Rienzo1,8, Zora Modrusan3,8, Florian Gnad2,8, Thong T Nguyen3,8, Bijay S Jaiswal3,8, Lucian R Chirieac4, Daniele Sciaranghella1, Nhien Dao1, Corinne E Gustafson1, Kiara J Munir1, Jason A Hackney2, Amitabha Chaudhuri5, Ravi Gupta5, Joseph Guillory3, Karen Toy3, Connie Ha3, Ying-Jiun Chen3, Jeremy Stinson3, Subhra Chaudhuri3, Na Zhang3, Thomas D Wu2, David J Sugarbaker6, Frederic J de Sauvage7, William G Richards1 & Somasekar Seshagiri3
We analyzed transcriptomes (n = 211), whole exomes (n = 99) and targeted exomes (n = 103) from 216 malignant pleural mesothelioma (MPM) tumors. Using RNA-seq data, we identified four distinct molecular subtypes: sarcomatoid, epithelioid, biphasic-epithelioid (biphasic-E) and biphasic-sarcomatoid (biphasic-S). Through exome analysis, we found BAP1, NF2, TP53, SETD2, DDX3X, ULK2, RYR2, CFAP45, SETDB1 and DDX51 to be significantly mutated (q-score ≥ 0.8) in MPMs. We identified recurrent mutations in several genes, including SF3B1 (~2%; 4/216) and TRAF7 (~2%; 5/216). SF3B1-mutant samples showed a splicing profile distinct from that of wild-type tumors. TRAF7 alterations occurred primarily in the WD40 domain and were, except in one case, mutually exclusive with NF2 alterations. We found recurrent gene fusions and splice alterations to be frequent mechanisms for inactivation of NF2, BAP1 and SETD2. Through integrated analyses, we identified alterations in Hippo, mTOR, histone methylation, RNA helicase and p53 signaling pathways in MPMs.