Cardiofaciocutaneous syndrome is a genetic disorder characterized by congenital heart disease, developmental delays and ectodermal abnormalities. Cardiofaciocutaneous syndrome is caused by pathogenic variants in the genes of the RAS/MAPK pathway, particularly BRAF. However, the mechanism by which congenital heart defects arise in RASopathy patients is still poorly understood. Therefore, using non-integrating episomal vectors, we generated three hiPSC clones from peripheral blood mononuclear cells from a 33-year old male carrying a c.1897 T > C missense variant in the BRAF gene, who was born with pulmonary stenosis, tricuspid atresia and hypoplastic right ventricle, consistent with a functional single ventricle.

Familial hypercholesterolemia is an autosomal dominant genetic disorder that often leads to abnormally high cholesterol levels in the body, which is closely related to early-onset coronary heart disease. LDLR gene mutation is the most common cause of familial hypercholesterolemia. In this study, we established an induced pluripotent stem cell (iPSC) line from a familial hypercholesterolemia patient harboring the c.1883delT heterozygous mutation in LDLR gene using non-integrative Sendai virus. This cell line carried the LDLR frameshift mutation, expressed pluripotency markers, showed the normal karyotype (46XX) and maintained the ability to differentiate into the three germ layers in vitro.

The establishment of well characterized control iPSC lines is essential for robust, reproducible research across laboratories. We used CRISPR/Cas9 to derive an isogeneic control line from a patient-derived iPSC line carrying a mutation in the NEFL gene (E396K). After correction of the E396K mutation, UCSFi003-A (WTD) exhibits multi-lineage differentiation potential, a normal karyotype, no large genomic abnormalities, and has consents for public distribution of cells and genomic data.

Up to 40 % of genetic variants identified in inherited arrhythmia syndromes (IAS) are classified as variants of uncertain significance (VUS) due to limited clinical and functional evidence. In Brugada syndrome (BrS), this challenge is further compounded by its polygenic nature, variable expressivity, and incomplete penetrance. Functional characterization in relevant disease models, such as human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), is essential for VUS reclassification. Here, using conventional CRISPR/Cas9, we established two isogenic hiPSC lines harboring the BrS-associated CACNA1C c.989C > T (p.Thr330Met) variant in homozygous and heterozygous configurations to enable future functional assessment.

Advanced age is a significant risk factor for cardiovascular diseases. Previously, we reported two female human induced pluripotent stem cell (hiPSC) lines. Here, we report generation and characterization of two hiPSC lines from peripheral blood mononuclear cells (PBMCs) obtained from young (18-year-old) and older (80-year-old) male donors. The two male hiPSC lines express pluripotency markers, possess normal (46, XY) karyotypes, and have trilineage differentiation potential. Both lines genetically match their parental PBMCs. These lines provide a vital resource for regenerative medicine and development of human-specific models to understand aging-associated diseases and to investigate the epigenetic mechanisms that are involved.

CHARGE syndrome is a multisystem neurodevelopmental disorder characterized by coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities. The CHD7 gene is the causal gene. A human iPSC line harboring a de novo heterozygous CHD7 mutation (c.3982C>T) was generated from peripheral blood mononuclear cells of a patient with CHARGE syndrome. This iPSC line exhibited typical human embryonic stem cell-like morphology, pluripotent markers, normal karyotype, and could differentiate into the three germ layers. This iPSC line is valuable for studying disease mechanisms and conducting drug screening in patient with CHARGE syndrome.

An expanded CTG repeat in intron 2 of the transcription factor 4 (TCF4) gene is the main cause of Fuchs endothelial corneal dystrophy (FECD), a complex corneal disease. The prevailing paradigm is that the expanded repeat exerts toxic effects, resulting in corneal endothelium degeneration. Here we explored the use of CRISPR/Cas9-mediated, non-homologous end-joining (NHEJ) for disease-modeling purposes, by performing a biallelic excision of the CTG18.1 expansion in two FECD- and one control-derived induced pluripotent stem cell lines (iPSCs). The three Δ/Δ CTG18.1 lines generated by this study provide a platform to investigate the CTG18.1 contribution to FECD pathogenesis.

MIC13 is essential for cristae formation and functions as a key component of the large mitochondrial multi subunit MICOS complex. Mutations in MIC13 causes severe mitochondrial disease called mitochondrial hepato-encephalopathy. In this study, we describe the generation of a human induced pluripotent stem cell (iPSC) line carrying a patient-specific MIC13 mutation, introduced using a CRISPR/Cas knock-in approach. The resulting iPSC line will provide a valuable model to study the pediatric severe mitochondrial disease and to determine the pathological mechanisms as well as to facilitate the identification of potential therapeutic targets in the future.

Xeroderma pigmentosum group A (XPA) is caused by defects in the nucleotide excision repair (NER) pathway, which is essential for repairing UV-induced DNA damage. Mutations in XPA impair lesion recognition and repair, resulting in mutation accumulation, genomic instability, and a high risk of skin cancers. In this study, we generated a CRISPR/Cas9-engineered human induced pluripotent stem cell (iPSC) line, WTSIi018-B-30, carrying a homozygous single nucleotide variant in exon 3 of XPA. The edited iPSCs retained normal morphology, expressed pluripotency markers, and differentiated into all three germ layers. This mutant iPSC line provides a robust isogenic model to dissect the molecular consequences of XPA deficiency and to explore therapeutic strategies for XPA-associated diseases.

Mutations in ADAR1 (Adenosine deaminase acting on RNA 1) and IFIH1 (Interferon Induced With Helicase C Domain 1) are associated with Aicardi-Goutières syndrome (AGS), a genetically determined inflammatory disorder particularly affecting the brain and skin. Here, we generated induced pluripotent stem cells (iPSCs) from one patient carrying compound heterozygous loss-of-function mutations in ADAR1 (PC138/AGS0788.1: c.577C > G p.(Pro193Ala) and c.1386_1390del p.(Asp462Glufs*2)), and one individual carrying a heterozygous gain-of-function mutation in IFIH1 (PC139/AGS2177.1: c.2336G > A p.(Arg779His)). Cells from these patients were reprogrammed by episomal transfection, had normal karyotype, expressed pluripotency markers and were able to differentiate into the three germ cell layers.

Primary fibroblasts were obtained from the dermal tissue from a healthy 50-year-old male donor and reprogrammed into induced pluripotent stem cells (iPSCs) using electroporation of reprogramming plasmids. The undifferentiated state of iPSCs was confirmed by immunofluorescence and flow cytometry analysis of stem cell markers, including TRA-1-60, Nanog, SOX2, and OCT4. The cells exhibited a normal karyotype. To evaluate their differentiation potential, the iPSCs were subcutaneously injected into immunodeficient mice, resulting in teratoma formation containing representative tissues of all three germ layers: endoderm, mesoderm, and ectoderm.

The MUi040-A human induced pluripotent stem cell (hiPSC) line was established from CD34 + hematopoietic stem cells of a male patient with senile amyloidosis. Patient carries a unique chromosome inversion at bands 9p12 and 9q13, which is one of the most common variants of the normal karyotype of chromosome 9 (inv[9]). This hiPSC line maintains an identical karyotype to that of the parental cells. MUi040-A expressed pluripotency markers and demonstrated the capacity to differentiate into all three germ layers. This cell line offers a valuable in vitro for studying the pathophysiology of senile systemic amyloidosis and for evaluating potential therapeutic approaches.

The human SLC6A1 gene encodes a Na- and Cl-dependent GABA (gamma-aminobutyric acid) transporter protein, GAT1, thought to act as a key mediator of the presynaptic GABA reuptake by neurons and astrocytes. We generated and characterised an induced pluripotent stem cell (iPSC) line from the fibroblasts of a neurodevelopmental disorder-affected boy, carrying a disease-causing variant in GAT1 (G307R), likely affecting neurotransmitter membrane permeation and intracellular trafficking of the transporter. This iPSC line exhibits typical human iPSCs features, expression of pluripotency-associated marker genes, ability to give rise to cells representing three embryonic germ layers, and a normal karyotype. We expect this iPSC line to aid in the in vitro modelling of, and development of precision therapies for, debilitating neurodevelopmental conditions caused by the variants in the SLC6A1 gene.

Alveolar rhabdomyosarcoma (ARMS) is an aggressive soft tissue sarcoma typically driven by the oncofusion protein PAX3::FOXO1 (P3F). Despite ARMS tumor histology and transcriptome resembling skeletal muscle, these tumors arise in areas devoid of skeletal muscle, indicating that non-myogenic cells can give rise to ARMS. Our lab demonstrated that endothelial progenitors are a cell of origin for rhabdomyosarcoma. Here we provide a protocol for generating iPSC-derived alveolar rhabdomyosarcoma cells (iARMS) during endothelial directed differentiation through enforced expression of P3F. This model allows for dissection of how P3F mediates transformation of endothelial progenitors into aggressive myogenic tumors.

ATRX is a chromatin-remodelling protein associated with neurodevelopmental disorders and gliomas, forming distinct nuclear foci associated with chromatin organization and phase-separated nuclear compartments. To visualize ATRX dynamics in live cells, we generated a human iPS cell (hiPSC) line with EGFP knocked in at the ATRX N-terminus using CRISPR/Cas12a-mediated genome editing. The modified hiPSCs retained pluripotency, normal karyotype, and trilineage differentiation potential. EGFP-ATRX localized to discrete nuclear foci, consistent with the phase-separated condensates described for ATRX, enabling real-time visualization of its chromatin association. This reporter line offers a valuable tool for studying ATRX function during differentiation and chromatin architecture development.

Drusen are extracellular deposits between the retinal pigment epithelium and Bruch's membrane, commonly linked to age-related macular degeneration (AMD). However, their presence in younger individuals offers a unique opportunity to study early disease mechanisms before extensive degeneration. We generated two human induced pluripotent stem cell (hiPSC) lines from siblings' peripheral blood mononuclear cells-one with early-onset bilateral drusen and the other unaffected. This genetically matched iPSC pair enables investigation of early drusen associated pathological changes driving retinal disease development.

Phospholamban (PLN) cardiomyopathy, caused by the deletion of arginine 14 in PLN (PLN-R14del), is associated with both dilated and arrhythmogenic cardiomyopathy, often manifesting early in life. Interestingly, some carriers remain asymptomatic with a normal life span. The mechanisms underlying disease progression remain unclear. We generated human induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells of two asymptomatic Greek PLN-R14del carriers and one non-carrier relative. These iPSC lines exhibit typical morphology and markers of undifferentiated hPSC state, providing an in vitro platform to investigate disease mechanisms and gain insights into the patient-specific onset and progression of PLN-R14del cardiomyopathy.

Spinocerebellar ataxia type 15/16 (SCA15/16) is a rare neurodegenerative disorder caused by heterozygous deletions of ITPR1, leading to haploinsufficiency of the encoded endoplasmic reticulum membrane calcium channel. Patients present with progressive gait disturbances, abnormal eye movements, difficulties with speech and swallowing, and tremors associated with atrophy of the cerebellum. Using CRISPR/Cas9 technology, we generated ITPR1 and isogenic control induced pluripotent stem cell (iPSC) lines from PGP1 iPSCs for SCA15/16 model development. The clones were genotyped, karyotyped, and assessed for pluripotency and differentiation potential.

Cardiomyopathies are a major contributor to cardiovascular mortality and are frequently linked to abnormalities in intercalated discs, which coordinate mechanical and electrical signaling between cardiomyocytes. The Nebulin-Related Anchoring Protein (NRAP), a key component of these structures, is essential for myofibril formation and force transmission. In various cardiac diseases such as cardiomyopathies with differing genetic mutations, NRAP protein abundance is increased, yet the functional consequences of this expression change remain insufficiently characterized. To investigate the outcome of NRAP-overexpression (NRAP-OE) on cardiac development and disease, we established a human induced pluripotent stem cell (hiPSC) line with stable and specific NRAP-OE in cardiomyocytes using CRISPR-Cas9-based genome editing. The resulting line was rigorously validated for chromosomal integrity, pluripotency markers, absence of off-target effects and mycoplasma contamination, as well as its capacity for trilineage differentiation. This NRAP-OE model offers a novel platform for investigating how increased NRAP levels influence cardiomyocyte structure and function, and may provide insight into its role in the pathogenesis of cardiomyopathy.

The RPE65 gene encodes a key enzyme in the visual cycle, a process essential for vision. While biallelic variants are known to cause severe, autosomal recessive, early-onset inherited retinal disease (IRD), we recently implicated a monoallelic founder variant in RPE65 c.1555G>A p.(E519K) in an autosomal dominant adult-onset maculopathy, a distinct IRD phenotype. Blood samples from three patients who are heterozygous for this novel missense variant were used to generate induced pluripotent stem cells (iPSCs). These iPSCs have been thoroughly characterized and will be differentiated into various retinal cell types to investigate the underlying disease mechanisms and assess potential therapeutic strategies.

TYR encodes tyrosinase, the enzyme catalysing the initial steps of melanin biosynthesis in melanocytes and retinal pigment epithelia (RPE). TYR c.1205G>A (p.Arg402Gln) is a common genetic variant associated with several pigmentation traits. Notably, when this variant is encountered in specific haplotypic backgrounds in the homozygous state, it predisposes to albinism. We generated an induced pluripotent stem cell (iPSC) line from an affected individual carrying such a homozygous genotype (UMANi255-A), and then used CRISPR-Cas9 to correct the TYR c.1205G>A variant (UMANi255-A-1). The resulting iPSC lines demonstrate capacity for multi-lineage differentiation, providing a useful in vitro model for studying pigmentation biology.