Repository NIGMS Human Genetic Cell Repository
Subcollection Heritable Diseases
Class Disorders of Connective Tissue, Muscle, and Bone
Biopsy Source Arm
Cell Type Fibroblast
Tissue Type Skin
Transformant Untransformed
Race Caucasian
Country of Origin USA
Family Member 3
Relation to Proband proband
Confirmation Clinical summary/Case history
ISCN 46,XY.arr(1-22)x2,(XY)x1
Species Homo sapiens
Common Name Human
Remarks Clinically affected; born after full term uncomplicated pregnancy; rolled over at 6 months old; began babbling at 9 months old; by 12 months old, there was marked muscle atrophy and weakness; absent deep tendon reflexes; constipation; donor subject has 3 copies of the SMN2 gene (data from several sources including Stabley et al. 2015, PMID 26247043); PCR analysis showed that this donor subject is homozygous for the deletion of exons 7 and 8 in the SMN1 gene; similarly affected brother (not in repository); mother is GM03814 (Fibro)/GM24474 (iPSC); father is GM03815 (Fibro); see GM23240 (iPSC - lentiviral) and GM24468 (iPSC - episomal); previously classified as SMA I, but data such as onset features and SMN2 dosage in the proband supported re-classification to SMA II.
PDL at Freeze 6.99
Passage Frozen 5
 
IDENTIFICATION OF SPECIES OF ORIGIN Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis
 
Gene SMN1
Chromosomal Location 5q12.2-q13.3
Allelic Variant 1 exons 7 and 8 deleted; SPINAL MUSCULAR ATROPHY, TYPE I
Identified Mutation EX7-8DEL
 
Gene SMN1
Chromosomal Location 5q12.2-q13.3
Allelic Variant 2 exons 7 and 8 deleted; SPINAL MUSCULAR ATROPHY, TYPE I
Identified Mutation EX7-8DEL
Remark Clinically affected; born after full term uncomplicated pregnancy; rolled over at 6 months old; began babbling at 9 months old; by 12 months old, there was marked muscle atrophy and weakness; absent deep tendon reflexes; constipation; donor subject has 3 copies of the SMN2 gene (data from several sources including Stabley et al. 2015, PMID 26247043); PCR analysis showed that this donor subject is homozygous for the deletion of exons 7 and 8 in the SMN1 gene; similarly affected brother (not in repository); mother is GM03814 (Fibro)/GM24474 (iPSC); father is GM03815 (Fibro); see GM23240 (iPSC - lentiviral) and GM24468 (iPSC - episomal); previously classified as SMA I, but data such as onset features and SMN2 dosage in the proband supported re-classification to SMA II.
Patil NA, Karas JA, Turner BJ, Shabanpoor F, Thiol-Cyanobenzothiazole Ligation for the Efficient Preparation of Peptide-PNA Conjugates Bioconjugate chemistry: 2019
PubMed ID: 30645945
 
Ottesen EW, Luo D, Seo J, Singh NN, Singh RN, Human Survival Motor Neuron genes generate a vast repertoire of circular RNAs Nucleic acids research: 2018
PubMed ID: 30698797
 
Garcia-Lopez A1, Tessaro F2, Jonker HRA3, Wacker A3, Richter C3, Comte A4, Berntenis N5, Schmucki R5, Hatje K5, Petermann O2, Chiriano G2, Perozzo R2, Sciarra D2, Konieczny P6,7, Faustino I8, Fournet G4, Orozco M8, Artero R6,7, Metzger F5, Ebeling M5, Goekjian P4, Joseph B4, Schwalbe H3, Scapozza L, Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes Nature Communications 9:2032 2018
PubMed ID: 29795225
 
Dayangac-Erden D1, Gur-Dedeoglu B2, Eskici FN1, Oztemur-Islakoglu Y2, Erdem-Ozdamar S3., Do Perineuronal Net Elements Contribute to Pathophysiology of Spinal Muscular Atrophy? In Vitro and Transcriptomics Insights OMICS A Journal of Integrative Biology9:2032 2018
PubMed ID: 30106667
 
Singh NN, Luo D, Singh RN, Pre-mRNA Splicing Modulation by Antisense Oligonucleotides Methods in molecular biology (Clifton, NJ)1828:415-437 2018
PubMed ID: 30171557
 
Touznik A, Maruyama R, Yokota T, In Vitro Evaluation of Antisense-Mediated Exon Inclusion for Spinal Muscular Atrophy Methods in molecular biology (Clifton, NJ)1828:439-454 2018
PubMed ID: 30171558
 
Sapaly D, Dos Santos M, Delers P, Biondi O, Quérol G, Houdebine L, Khoobarry K, Girardet F, Burlet P, Armand AS, Chanoine C, Bureau JF, Charbonnier F, Lefebvre S, Small-molecule flunarizine increases SMN protein in nuclear Cajal bodies and motor function in a mouse model of spinal muscular atrophy Scientific reports8:2075 2017
PubMed ID: 29391529
 
Stabley DL, Harris AW, Holbrook J, Chubbs NJ, Lozo KW, Crawford TO, Swoboda KJ, Funanage VL, Wang W, Mackenzie W, Scavina M, Sol-Church K, Butchbach ME, SMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR Molecular genetics & genomic medicine3:248-57 2015
PubMed ID: 26247043
 
Xu CC, Denton KR, Wang ZB, Zhang X, Li XJ, Abnormal mitochondrial transport and morphology as early pathological changes in human models of spinal muscular atrophy Disease models & mechanisms9:39-49 2015
PubMed ID: 26586529
 
Mack SG, Cook DJ, Dhurjati P, Butchbach ME, Systems biology investigation of cAMP modulation to increase SMN levels for the treatment of spinal muscular atrophy PloS one9:e115473 2014
PubMed ID: 25514431
 
Liu ML, Zang T, Zou Y, Chang JC, Gibson JR, Huber KM, Zhang CL, Small molecules enable neurogenin 2 to efficiently convert human fibroblasts into cholinergic neurons Nature communications4:2183 2013
PubMed ID: 23873306
 
Anderton RS, Price LL, Turner BJ, Meloni BP, Mitrpant C, Mastaglia FL, Goh C, Wilton SD, Boulos S, Co-regulation of SMN and Bcl-xL Expression: Implications for Neuroprotection in Spinal Muscular Atrophy Neuroscience4:2183 2012
PubMed ID: 22732506
 
Liu J, Hu J, Corey DR, Expanding the action of duplex RNAs into the nucleus: redirecting alternative splicing Nucleic acids research40:1240-50 2011
PubMed ID: 21948593
 
Anderton RS, Meloni BP, Mastaglia FL, Greene WK, Boulos S, Survival of motor neuron protein over-expression prevents calpain-mediated cleavage and activation of procaspase-3 in differentiated human SH-SY5Y cells Neuroscience181:226-33 2010
PubMed ID: 21333717
 
Ebert, A.D. and Svendsen, C.N., Stem Cell Model of Spinal Muscular Atrophy Arch Neurol67(6):665-669 2010
PubMed ID: 20558385
 
Ebert, A.D.; Yu, J.; Ferrill, F.R.; Mattis, V.B.; Lorson, C.L.; Thomson, J.A.; and Svendsen, C.N., Induced pluripotent stem cells from a spinal muscular atrophy patient Nature457(7227):277-80 2009
PubMed ID: 19098894
 
Thurmond J1, Butchbach ME, Palomo M, Pease B, Rao M, Bedell L, Keyvan M, Pai G, Mishra R, Haraldsson M, Andresson T, Bragason G, Thosteinsdottir M, Bjornsson JM, Coovert DD, Burghes AH, Gurney ME, Singh J., Synthesis and biological evaluation of novel 2,4-diaminoquinazoline derivatives as SMN2 promoter activators for the potential treatment of spinal muscular atrophy. J Med Chem51(3):449-69 2008
PubMed ID: 18205293
 
Thi Man N, Humphrey E, Lam LT, Fuller HR, Lynch TA, Sewry CA, Goodwin PR, Mackenzie AE, Morris GE, A two-site ELISA can quantify upregulation of SMN protein by drugs for spinal muscular atrophy Neurology51(3):449-69 2008
PubMed ID: 18633133
 
Simard LR, Bélanger MC, Morissette S, Wride M, Prior TW, Swoboda KJ, Preclinical validation of a multiplex real-time assay to quantify SMN mRNA in patients with SMA Neurology68:451-6 2007
PubMed ID: 17283322
 
Novoyatleva T1, Heinrich B, Tang Y, Benderska N, Butchbach ME, Lorson CL, Lorson MA, Ben-Dov C, Fehlbaum P, Bracco L, Burghes AH, Bollen M, Stamm S., Protein phosphatase 1 binds to the RNA recognition motif of several splicing factors and regulates alternative pre-mRNA processing. Hum Mol Genet17(1):52-70 2007
PubMed ID: 17913700
 
Singh NK, Singh NN, Androphy EJ, Singh RN, Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique silencer element located in the last intron Molecular and cellular biology26:1333-46 2006
PubMed ID: 16449646
 
Avila AM, Burnett BG, Taye AA, Gabanella F, Knight MA, Hartenstein P, Cizman Z, Di Prospero NA, Pellizzoni L, Fischbeck KH, Sumner CJ, Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy The Journal of clinical investigation117:659-71 2006
PubMed ID: 17318264
 
Kernochan LE, Russo ML, Woodling NS, Huynh TN, Avila AM, Fischbeck KH, Sumner CJ, The role of histone acetylation in SMN gene expression. Hum Mol Genet14(9):1171-82 2005
PubMed ID: 15772088
 
Wan L, Battle DJ, Yong J, Gubitz AK, Kolb SJ, Wang J, Dreyfuss G, The survival of motor neurons protein determines the capacity for snRNP assembly: biochemical deficiency in spinal muscular atrophy Molecular and cellular biology25:5543-51 2005
PubMed ID: 15964810
 
Kelley BP, Lunn MR, Root DE, Flaherty SP, Martino AM, Stockwell BR, A flexible data analysis tool for chemical genetic screens. Chem Biol11(11):1495-503 2004
PubMed ID: 15556000
 
Lunn MR, Root DE, Martino AM, Flaherty SP, Kelley BP, Coovert DD, Burghes AH, Man NT, Morris GE, Zhou J, Androphy EJ, Sumner CJ, Stockwell BR, Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism. Chem Biol11(11):1489-93 2004
PubMed ID: 15555999
 
Sumner CJ, Huynh TN, Markowitz JA, Perhac JS, Hill B, Coovert DD, Schussler K, Chen X, Jarecki J, Burghes AH, Taylor JP, and Fischbeck KH. , Valproic acid increases SMN levels in spinal muscular atrophy patient cells. Ann Neurol54:647-654 2003
PubMed ID: 14595654
 
DiDonato CJ, Parks RJ, Kothary R, Development of a gene therapy strategy for the restoration of survival motor neuron protein expression: implications for spinal muscular atrophy therapy. Hum Gene Ther14(2):179-88 2003
PubMed ID: 12614569
 
Gangwani L, Mikrut M, Theroux S, Sharma M, Davis RJ, Spinal muscular atrophy disrupts the interaction of ZPR1 with the SMN protein. Nat Cell Biol3(4):376-83 2001
PubMed ID: 11283611
 
Scudiero DA, Polinsky RJ, Brumback RA, Tarone RE, Nee LE, Robbins JH, Alzheimer disease fibroblasts are hypersensitive to the lethal effects of a DNA-damaging chemical. Mutat Res159:125-31 1986
PubMed ID: 3941662
No data is available
Passage Frozen 5
Split Ratio 1:5
Temperature 37 C
Percent CO2 5%
Percent O2 AMBIENT
Medium Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids
Serum 15% fetal bovine serum Not inactivated