Holt-Oram Syndrome

Holt-Oram syndrome, commonly known as the heart-hand syndrome, is a type of autosomal dominant disorder that is characterized by heart defects and issues with the upper limbs. Protheragen is a specialized research service provider for rare cardiovascular disorders such as Holt-Oram syndrome. We are passionate about transforming scientific knowledge into practical therapeutic interventions for rare cardiovascular conditions, so we customize our comprehensive services to best suit your requirements.

Introduction to Holt-Oram Syndrome

Holt-Oram syndrome manifests with anomalies of the upper limbs, congenital heart defects, and cardiac electrical conduction abnormalities.

In individuals with Holt-Oram syndrome, congenital heart defects are seen in 75% of individuals, most frequently involving the septum. Atrial septal defect (ASD) and ventricular septal defect (VSD) may be found in variable numbers, size, and position. Holt-Oram syndrome is the most known among the heart-hand syndromes, and the estimated prevalence ranges from 0.7 to 1 per 100,000 births.

Fig.1 The presence of a secundum ASD. (Gupta, M., et al., 2022)

Pathogenesis of Holt-Oram Syndrome

Holt-Oram syndrome has an autosomal dominant inheritance pattern. A heterozygous mutation at the TBX5 gene located on 12q24.1 is known to produce Holt-Oram syndrome. This TBX5 gene provides the coding sequence for a protein T-box5 which acts as a transcription factor that controls the activity of other genes associated with heart and limb development. In particular, it plays an essential role in cardiac septation as well as in the osteogenesis of the upper limbs' bones. Greater than eighty-five percent of cases of Holt-Oram syndrome observed have been noted to have the mutated TBX5 gene.

Fig.2 The distribution of missense and truncated variants in TBX5. (Møller Nielsen, A. K., et al., 2024)

Therapeutics Development for Holt-Oram Syndrome

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a therapy plan recommendation. For guidance on therapy options, please visit a regular hospital.

Our Services

At every step of your project, our team works efficiently to provide you with the most advanced technical support. We provide an integrated solution to assist in the preclinical phases of drug research and development which includes the development of diagnostics, therapeutics, and disease models. To integrate your discoveries into real-world applications, our tailored services are crafted to enhance your research efforts.

Therapeutic Development Services

Diverse Platforms

• Small Molecule Drug Development
• Gene Therapy Development
• Therapeutic Peptide Development

• Cell Therapy Development
• Therapeutic Antibody Development
• Therapeutic Protein Development

Animal Model Development for Holt-Oram Syndrome

Animal models are provided with important pathology information about Holt-Oram syndrome and they have also been used to elucidate the disease's mechanisms and analyze its possible cures. Our company is distinguished by an unbending dedication to scientific quality and individualized service and it offers tailor-made animal model development services for research of Holt-Oram syndrome.

Genetically Engineered Models

Animal models are constructed using advanced genetic engineering techniques, to manipulate TBX5 expression and reproduce the syndrome's cardiac and limb abnormalities.

• Tbx5 conditional knockdown model
• Tbx5^del/+ model

• Tbx5^del/del model
• Other models

Protheragen's service portfolio extends to comprehensive preclinical study support, including pharmacokinetic research and drug safety evaluation. We understand that groundbreaking science requires precise methodologies, and we utilize advanced technologies to generate highly reliable data, ensuring that your research advances effectively. If you are interested in our services, please contact us for detailed information.

References

• Gupta, Mehak et al. "Holt-Oram Syndrome: An Incidental Diagnosis." Cureus 14.5 (2022): e24899.
• Møller Nielsen, Anne Kathrine et al. "TBX5 variants and cardiac phenotype: A systematic review of the literature and a novel variant." European journal of medical genetics 68 (2024): 104920.