Discovery 9 of 10


It turns out that the frequency of the variants responsible for the development of the symptoms of the disease in the Polish population is much more frequent than in the general (world) population.

Syndrome (SLOS), also known as congenital 7-dehydrocholesterol reductase deficiency, is characterized by numerous birth defects, as well as intellectual disability and many behavioral problems.The disease is caused by an inherited defect in cholesterol synthesis, due to a mutation in the DHCR7 gene (11q13.4). This leads to a deficiency of the enzyme 7-dehydrocholesterol reductase, which converts 7-dehydrocholesterol (7DHC) into cholesterol.

The global prevalence of SLOS is estimated at about 1:20,000–1: 60,000 cases, however, studies conducted in Central Europe (including Poland, the Czech Republic and Slovakia) suggest that in these regions the occurrence of the disease may be much more frequent (even below 1:10,000). According to OMIM, in the Polish population the frequency of the DHCR7 gene mutation is between 1.26 and 1.32, and the frequency of the disease is 1: 2 300–1: 3 937.

It is assumed that the Smith-Lemli-Opitz syndrome is one of the most common metabolic diseases in Poland, and being a carrier is much more common than in other countries. The MAF (minor allele frequency) for the variant designated in the literature as W151X is globally 0.07% (GnomAD v3.1.1), but in the Polish population it is estimated at at least 1.2%.

Interesting fact: the disease was originally described as RSH Syndrome, from the first letters of the surnames of Dr. Smith's three patients, but further research involving another two specialists and ethical considerations (patient protection - preventing their identification) made the disease entered the medical literature as Smith-Lemli syndrome -Opitz.

The Thousand PolishGenomes Project - a national database of Polish variant allele frequencies" is a unique scientific project, the aim of which was to create the first database of genetic variants of Poles and Polish women. The presented results come from this project.

Find out more about SLOS

First description of SLOS from 1964:

P.S. Of course, there exists data that is less extensive than WGS analyzes from other populations, but with a much larger sample size, for example in 23andMe or FTDNA collections. In this project, however, we focused only on data from genome-wide projects. Remember that the The Thousand PolishGenomes project is open to more discoveries by other research groups in the upcoming groups, and the presented results are only the tip of the iceberg.