Repository NIGMS Human Genetic Cell Repository
Subcollection Heritable Diseases
Protocols Protocol PDF
Biopsy Source Skin
Cell Type Stem cell
Tissue Type Induced pluripotent stem cell
Transformant Reprogrammed (Retroviral)
Race Asian
Hispanic Ethnicity Not Hispanic/Latino
Ethnicity Chinese
Country of Origin USA
Family Member 1
Family History N
Relation to Proband proband
Confirmation Karyotypic analysis and Molecular characterization
ISCN 46,XX[25]
Species Homo sapiens
Common Name Human
Remarks Induced pluripotent stem cell derived from dermal skin fibroblasts (collected from the leg); subject is clinically affected; EKG test: QT prolongation, 493 ms; FISH results at time of submission: 46 XX; comprehensive open reading frame and splice site analysis of protein-coding exons was conducted using polymerase chain reaction, denaturing high performance liquid chromatography, and DNA sequencing of genomic DNA from the subject; sequencing revealed a missense mutation in exon 6 of the KCNH2 (HERG) gene: 1264G>A, A422T; this novel pathogenic variant is localized at S1 in the transmembrane-spanning domain of the IKr potassium channel alpha subunit encoded by KCNH2; it is not known if parents had LQT mutation - parental samples were unavailable. This iPSC line was submitted by Dr. Bruce R. Conklin (Gladstone Institute of Cardiovascular Disease, UCSF).
Passage Frozen 35
 
Induced Pluripotent Stem Cell The frozen cell line submitted to the Repository was recovered and expanded. The expanded line was evaluated for viability surface antigen expression and alkaline phosphatase activity. Pluripotency was assessed via embryoid body (EB) formation and PluriTest. Steady-state mRNA expression patterns of undifferentiated iPSC and EBs were determined via real-time PCR. Characterization data are included in the Certificate of Analysis.
 
Gene KCNH2
Chromosomal Location 7q36.1
Allelic Variant 1 missense; LONG QT SYNDROME 2; LQT2
Identified Mutation ALA422THR; Congenital long QT syndrome is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncope, seizure, or sudden death (Jongbloed et al., 1999).
Remark Induced pluripotent stem cell derived from dermal skin fibroblasts (collected from the leg); subject is clinically affected; EKG test: QT prolongation, 493 ms; FISH results at time of submission: 46 XX; comprehensive open reading frame and splice site analysis of protein-coding exons was conducted using polymerase chain reaction, denaturing high performance liquid chromatography, and DNA sequencing of genomic DNA from the subject; sequencing revealed a missense mutation in exon 6 of the KCNH2 (HERG) gene: 1264G>A, A422T; this novel pathogenic variant is localized at S1 in the transmembrane-spanning domain of the IKr potassium channel alpha subunit encoded by KCNH2; it is not known if parents had LQT mutation - parental samples were unavailable. This iPSC line was submitted by Dr. Bruce R. Conklin (Gladstone Institute of Cardiovascular Disease, UCSF).
Spencer CI, Baba S, Nakamura K, Hua EA, Sears MA, Fu CC, Zhang J, Balijepalli S, Tomoda K, Hayashi Y, Lizarraga P, Wojciak J, Scheinman MM, Aalto-Setälä K, Makielski JC, January CT, Healy KE, Kamp TJ, Yamanaka S, Conklin BR, Calcium transients closely reflect prolonged action potentials in iPSC models of inherited cardiac arrhythmia Stem cell reports3:269-81 2013
PubMed ID: 25254341
 
Tester DJ, Will ML, Haglund CM, Ackerman MJ, Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing Heart rhythm : the official journal of the Heart Rhythm Society2:507-17 2004
PubMed ID: 15840476
No data is available
Passage Frozen 35
Temperature 37 C
Percent CO2 5%
Percent O2 AMBIENT
Medium Check Folder
Serum 20% Knock-out Serum Replacement
Substrate Matrigel