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Project Description

Please note that we are a research service provider, not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.

Nance-Horan Syndrome (NHS)

Nance-Horan Syndrome (NHS) is an X-linked dominant disorder with a prevalence that remains uncertain due to its rarity and underdiagnosis. As a leading service provider in the field of rare genetic disorders, Protheragen is focused on the development of diagnostics and therapeutics for Nance-Horan syndrome.

Overview of Nance-Horan Syndrome (NHS)

Nance-Horan Syndrome (NHS) is a rare X-linked genetic disorder characterized by a spectrum of ocular and dental anomalies, mental retardation, and unusual facial contortion. The syndrome is caused by mutations in the NHS gene located on the X chromosome Xp22.13 and was first described in 1974. The conserved NHS gene in vertebrates is expressed in the brain, retina, lens, tooth primordia, craniofacial mesenchyme, and heart. Congenital cataracts with nystagmus, microcornea, microphthalmia, glaucoma, and developmental delays with dental dysplasia in the form of screwdriver-shaped incisors, supernumerary teeth, and diastema are some of the key features of the disorder.

Pedigrees of three Nance-Horan Syndrome (NHS) families.

Fig.1 Pedigrees of three NHS families. (Guven Y., et al., 2023)

Diagnostics Development for Nance-Horan Syndrome

Molecular diagnosis of NHS is critical for the correct classification and therapeutic of the condition. As reported, Sanger sequencing is a frequently applied technique to analyse mutations of the NHS gene. This method enables the detection of point mutations, small deletions, and insertions. For example, a novel nonsense variant, c.2416 C > T; p.(Gln806), was discovered during the clinical diagnosis of a 10-year-old male cases with NHS.

Another highly sensitive technique is chromosomal microarray (CMA) which focuses on more extensive deletions or duplications of the genome containing the NHS gene. For instance, an 1.83-Mb interstitial microdeletion at Xp22.2p22.13 was detected in a 19-year-old male case with NHS which included the NHS gene along with many others. This technique is also applicable to complex genomic rearrangements which are assumed to be responsible for the demerit diversity of NHS.

Therapeutics Development for Nance-Horan Syndrome

Gene Replacement Therapy
The objective of gene replacement therapy is to add a functioning NHS gene into certain cells with the hope of restoring the desired protein activity. This method holds great potential for disorders originating from loss-of-function mutations. For instance, evidence has demonstrated that certain cellular defects are associated with the disorder, but introducing a properly functioning NHS gene to cells from NHS patients can resolve these issues.

Small Molecule and Biologics Development
Small molecules as well as biologics aimed at addressing the disrupted molecular pathways in NHS are also being developed. These therapies are meant to target the downstream effects of the mutations within the NHS gene. For instance, one study that was conducted recently reported the discovery of a small molecule that increases the stability of the NHS protein. Such a small molecule would be beneficial for some types of mutations.

Our Services

Protheragen develops complete therapies and diagnostics for Nance-Horan Syndrome and offers various services related to the disease. Using industry-leading technologies, our skilled scientific staff work towards understanding and finding therapeutics for this rare condition. We provide a number of services, for example:

Diagnostics Development

Karyotype Analysis Service
Omics Analysis Service
Biomarker Development Service
Artificial Intelligence Service
Customized Diagnostics Development

Therapeutic Development

Small Molecule Drug
Cell Therapy
Gene Therapy
Therapeutic Antibody
Therapeutic Peptide
Therapeutic Protein
Customized Therapy Development

Disease Models

Xcat mouse model: The model harbours a massive insertional mutation in the first intron of the Nhs1 gene which causes the expression of an alternative isoform containing exon 1A only. This model is able to reproduce some aspects of the disorder in humans, which includes congenital cataracts and the lens having a lower expression of Nhs1 protein.

Protheragen offers a suite of preclinical research services to support the development of novel therapies for NHS. Our services include:

Bioinformatics and Data Analysis: Advanced bioinformatics tools to analyze genetic data and identify potential therapeutic targets.
Genetic Modeling: Development of animal models carrying NHS gene mutations to study disease progression and evaluate therapeutic interventions.
Pharmacokinetics and Toxicology Studies: Comprehensive preclinical testing to assess the safety and pharmacokinetics of potential therapeutic agents.

If you are interested in our services, please feel free to contact us.

References

Guven, Yeliz, et al. "Nance-Horan Syndrome: characterization of dental, clinical and molecular features in three new families." BMC oral health 23.1 (2023): 314.
Li, Huajin, et al. "A novel small deletion in the NHS gene associated with Nance-Horan syndrome." Scientific Reports 8.1 (2018): 2398.