AG28340

AG28340 iPSC from Fibroblast

Description:

HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS
LAMIN A/C; LMNA

Affected:

Yes

Sex:

Male

Age:

14 YR (At Sampling)

Overview

Repository

NIA Aging Cell Culture Repository

Subcollection

Heritable Diseases

Protocols

Protocol PDF

Biopsy Source

Skin

Cell Type

Stem cell

Cell Subtype

Induced pluripotent stem cell

Transformant

Reprogrammed (Sendai)

Sample Source

iPSC from Fibroblast

Race

Black/African American

Relation to Proband

proband

Confirmation

Clinical summary/Case history

ISCN

46,XY[20]

Species

Homo sapiens

Common Name

Human

Remarks

Donor showed typical appearance including loss of subcutaneous fat, alopecia, osteoarthritis, and a grade II/VI systolic heart murmur. Donor subject has a de novo single base substitution, a C>T change at nucleotide 2036 (2036C>T), which results in a silent change at codon 608 [Gly608Gly (G608G)] in exon 11 of the Lamin A gene (LMNA). This substitution creates an exonic consensus splice donor sequence and results in activation of a cryptic splice site which in turn causes skipping of 150 bp of the LMNA mRNA leading to the deletion of 50 amino acids from the protein. This altered LMNA protein was detected on western blots [Eriksson et al., Nature 423:293 (2003)]. Stem cell line reprogrammed from parental fibroblast line AG11498. Researchers purchasing hiPSCs from the NIA Repository are responsible for any limited use label licenses (LULLs) applicable to the cell line purchased. The applicable LULL to this line is Sendai-CytoTune.

Characterizations

Passage Frozen

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. 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

LMNA

Chromosomal Location

1q21.2

Allelic Variant 1

150330.0022; HUTCHINSON-GILFORD PROGERIA SYNDROME

Identified Mutation

GLY608GLY; Description: In 18 of 20 patients with classic Hutchinson-Gilford progeria syndrome (176670), Eriksson et al. [Nature 423: 293 (2003)] found an identical de novo single-base substitution, a C-to-T change resulting in a silent gly-to-gly mutation at codon 608 (G608G) within exon 11 of the LMNA gene. This substitution created an exonic consensus splice donor sequence and resulted in activation of a cryptic splice site and deletion of 50 basepairs of prelamin A. This mutation was not identified in any of the 16 parents available for testing.