Two papers: the cause of an often overlooked genetic disease

 Splicing defects are often overlooked because they may not change the production of amino acids and play an important role in rare inherited pituitary diseases

The pituitary gland is an important center of hormonal activity

In a recent study, Camper and his colleagues discovered splicing defects in POU1F1 in 6 families with children with congenital hormone deficiency

This research aroused the interest of Jacob Kitzman, assistant professor of human genetics, computational medicine, and bioinformatics at UMMS

 Kitzman recommends making and testing every possible mutation to find other mutations that can disrupt splicing similar to patient variants, and to understand the common factors of splicing disrupting mutations

 Kitzman said: "The splicing effect is usually difficult to predict, so we think it will be a good opportunity to use some of the methods developed by my team to systematically test thousands of variants at a time

The team found several variants that can disrupt splicing, but do not affect the amino acid sequence of the protein

"We have many variants in our genes, and it is difficult to distinguish which ones are harmful and which are benign

 Then, the team asked the collaborators to provide a series of variations from their patient's sequence

 This research also allows comparison of several software packages that predict splicing results, one of which stands out as the best predictor

"For people studying any disease, this kind of verification is more interesting

One of the challenges of studying rare diseases is finding patients, which requires extensive cooperation

"When researching rare diseases, it is very helpful to establish strong partnerships to identify and register patients whose participation is vital

In another recent collaborative study, 170 Argentine patients were screened for gene mutations of known hypopituitarism, and only 15% of patients had known gene mutations

Paper citation:

"High-throughput splicing assays identify missense and silent splice-disruptive POU1F1 variants underlying pituitary hormone deficiency," The American Journal of Human Genetics .

“Comprehensive identification of pathogenic gene variants in patients with neuroendocrine disorders,” Journal of Clinical Endocrinology and Metabolism.
? DOI: 10.
1210/clinem/dgab177