Current Landscape of iPSC Haplobanks.

The use of allogeneic induced pluripotent stem cell (iPSC)-derived cell therapies for regenerative medicine offers an affordable and realistic alternative to producing individual iPSC lines for each patient in need. Human Leukocyte Antigens (HLA)-homozygous iPSCs matched in hemi-similarity could provide cell therapies with reduced immune rejection covering a wide range of the population with a few iPSC lines. Several banks of HLA-homozygous iPSCs (haplobanks) have been established worldwide or are underway, to provide clinical grade starting material for cell therapies covering the most frequent HLA haplotypes for certain populations.

iPSC-Based Modeling of Variable Clinical Presentation in Hypertrophic Cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and a frequent cause of heart failure and sudden cardiac death. Our understanding of the genetic bases and pathogenic mechanisms underlying HCM has improved significantly in the recent past, but the combined effect of various pathogenic gene variants and the influence of genetic modifiers in disease manifestation are very poorly understood. Here, we set out to investigate genotype-phenotype relationships in 2 siblings with an extensive family history of HCM, both carrying a pathogenic truncating variant in the gene (p.

A Human Hereditary Cardiomyopathy Shares a Genetic Substrate With Bicuspid Aortic Valve.

Background: The complex genetics underlying human cardiac disease is evidenced by its heterogenous manifestation, multigenic basis, and sporadic occurrence. These features have hampered disease modeling and mechanistic understanding. Here, we show that 2 structural cardiac diseases, left ventricular noncompaction (LVNC) and bicuspid aortic valve, can be caused by a set of inherited heterozygous gene mutations affecting the NOTCH ligand regulator MIB1 (MINDBOMB1) and cosegregating genes.

Atypical cyclin P regulates cancer cell stemness through activation of the WNT pathway.

Purpose: Cancer stem cells represent a cancer cell subpopulation that has been found to be associated with metastasis and chemoresistance. Therefore, it is vital to identify mechanisms regulating cancer stemness. Previously, we have shown that the atypical cyclin P (CCNP), also known as CNTD2, is upregulated in lung and colorectal cancers and is associated with a worse clinical prognosis.

Inborn errors of metabolism: Lessons from iPSC models.

The possibility of reprogramming human somatic cells to pluripotency has opened unprecedented opportunities for creating genuinely human experimental models of disease. Inborn errors of metabolism (IEMs) constitute a greatly heterogeneous class of diseases that appear, in principle, especially suited to be modeled by iPSC-based technology. Indeed, dozens of IEMs have already been modeled to some extent using patient-specific iPSCs.

Trabeculated Myocardium in Hypertrophic Cardiomyopathy: Clinical Consequences.

Aims: Hypertrophic cardiomyopathy (HCM) is often accompanied by increased trabeculated myocardium (TM)-which clinical relevance is unknown. We aim to measure the left ventricular (LV) mass and proportion of trabeculation in an HCM population and to analyze its clinical implication.

Methods And Results: We evaluated 211 patients with HCM (mean age 47.

Persistence of müllerian derivatives, lymphangiectasis, hepatic failure, postaxial polydactyly, renal and craniofacial anomalies.

We describe 3 unrelated newborn males with a previously unreported constellation of congenital anomalies. All 3 died neonatally of hepatic failure. Clinically, they presented with a pattern of malformations characterized by prenatal linear growth deficiency, hypertrophied alveolar ridges, redundant nuchal skin, and postaxial polydactyly.

Flaccid paraplegia as complication of umbilical artery catheterization.

Two patients are described who acquired neonatal flaccid paraplegia associated with umbilical artery catheterization. Neurophysiologic studies demonstrated spinal cord injury at the level of T7 and below in Patient 1 and at the level of L1 and below in Patient 2. Deferred spinal cord magnetic resonance imaging confirmed regional spinal cord atrophy.

Congenital cutaneous candidiasis: report of four cases and review of the literature.

Congenital cutaneous candidiasis (CCC) is a rare disease acquired by an ascending route, liable to affect the offspring of pregnant women suffering from vulvovaginitis. The cutaneous lesions are present at birth or within the first hours of life. Some infants may present with respiratory distress or clinical signs of sepsis during the first 2 days of life.

[Trisomy 5p: a report of 2 cases].

Authors report two patients from different families who present similar abnormalities caused by an "almost complete" trisomy of the short arm of chromosome 5 [case No. 1: 46, XY, der (20), t (5; 20) (p11;p13), mat; case No.2: 46, XY, dup (5p)].