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Bardet-Biedl syndrome

What causes Bardet Biedl syndrome?

What causes Bardet Biedl syndrome?

Bardet-Biedl syndrome can result from mutations in at least 14 different genes (often called BBS genes). These genes are known or suspected to play critical roles in cell structures called cilia. Cilia are microscopic, finger-like projections that stick out from the surface of many types of cells.

Bardet-Biedl syndrome

The syndrome Pardt – Biddle (Bardet – Biedl syndrome), is a hereditary disease transmitted by heredity Alootozumih recessive. This syndrome is characterized by excessive weight gain , which usually appears in childhood and increases with age. Retinal atrophy appears first, and also in early childhood – as impaired night vision or in poor lighting conditions, which progresses to tubular vision and partial blindness in late adulthood. Additional fingers may appear on all four limbs or only some of them.

In most cases, a full sixth finger appears (after the pinky finger), and sometimes the finger is partially atrophied. The genitals can be very small, but the hormonal system often functions normally, and there have been several cases of Bardt-Biedl patients giving birth to healthy offspring. Most Bardt-Biedl patients have some degree of mental development disability, from the lowest degree of proper functioning to mental retardation.

Approximately 90% of cases have a kidney abnormality that varies in severity between patients, and this abnormality of the kidneys is represented by an abnormal location of the kidneys, small size or no presence at all, and also other less serious conditions. The heart defects described are not specific, but it is worth noting that they are various cases of general and/or local enlargement and/or thickening of the heart muscle, which are not necessarily associated with a congenital kidney defect or secondary complications, such as high blood pressure.

The prevalence of type 2 diabetes (non-insulin-related) is very high among Bardt-Biedl patients, and even among family members who do not show signs of the disease.

The great scientific importance of understanding the genetic cause of this disease, despite the relatively low prevalence of the disease in general, estimated at one case per 100,000 people (1:100,000), is due to the fact that some phenomena of this disease, such as obesity and diabetes, are common. In general, therefore, information about the genes that cause this disease is of great importance for understanding the genetic factor of complex diseases; However, there are some specific social groups, in which the prevalence of the disease is particularly high. It concerns an Arab population of Kuwait, Bedouin tribes in the Middle East and southern Palestine, as well as in New Poundland in Canada.

Bardt-Biedl disease, which was previously considered a recessive genetic disease, turns out to be a very diverse and complex disease, and to date at least eight chromosomal loci are known, in which the causative genes have been detected: 11q13 (BBS1), 16q21 (BBS2) , 3p13-p12 (BBS3), 15q22.3-q23 (BBS4), 2q31 (BBS5), 20p12 (BBS6). Other conditions, not mapped to any of these loci, demonstrate that other genes are associated with this disease.

BBS6 Bardet-Biedl disease is caused by a mutation in the MKKS gene in which other mutations cause a disease called McKusick-Kaufman syndrome, hydrometrocolpos, sixth finger and congenital heart defects. Recently, the genes responsible for BBS4, BBS2 and BBS1 have also been identified – which is the most common disease-causing gene.

That, while the protein produced by the gene for BBS6 shows a lot of similarity to the chaperonin gene, BBS4 and BBS2 BBS1 do not show any similarity to all known proteins, or known protein families; Also, no homology was found between these three genes; On the other hand, based on a limited homology between BBS1 and BBS2, it was possible to detect the BBS1 gene. The BBS7 and BBS8 genes were identified by a computerized search in the information list of proteins with partial homology to – BBS2 and BBS4, respectively. BBS5 and -BBS3 were recently identified, using a combination of positional cloning and comparative genomics.

One study, released in recent years, suggested the possibility of triple-allelic inheritance in Bardt-Biedl disease. The appearance of clinical symptoms of the disease, according to the results of this study, requires the presence of three mutations in at least two different genes. This intriguing hypothesis, which deviates from the accepted rules of inheritance for monogenic recessive diseases, has not been supported by other extensive research and still needs further proof.

The relationship between the different types of genes and mutations that cause Bardt-Biedl disease, and the clinical symptoms of the disease, is an important topic and is not yet clear. While some studies did not show any relationship, others showed potential differences in the extent and timing of obesity, as well as the extent and prevalence of the sixth finger phenomenon among different genes. At this stage of the research, prenatal diagnosis can be made, and BBS mutation carriers can be detected in most families in which the disease is present.

Symptoms of Bardet-Biedl Syndrome

The main signs are: obesity, pigmentary retinopathy, polydactyly, developmental delay to the point of mental retardation , smaller than average genitals in males and kidney defects.

People with this disease have a high risk of having congenital heart defects, type 2 diabetes , and high blood pressure (hypertension). The manifestations of the disease differ between and within families. The clinical diagnosis is based on the presence of at least three primary signs of the disease.

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