This web page was produced as an assignment for Genetics 677 an undergraduate course at UW-Madison
What is Bardet-Biedl Syndrome?
Bardet-Biedl syndrome is a rare genetic disorder. The typical age that diagnosis of the disease occurs varies due to the wide array of symptoms and different ages these symptoms can onset. The prevalence of this disease in North America and Europe is 1 in 140,000 to 1 in 160,000 newborns [1]. However, it is more prevalent in other areas in the world. The island of Newfoundland, located off the coast of Canada, has a prevalence of about 1 in 17,000 newborns [2]. It is even more frequent in the Bedouin population of Kuwait affecting 1 in 13,500 newborns [1].
Bardet-Biedl syndrome can causes a large variety of symptoms. The symptoms themselves vary from individual to individual even if they are from the same family. The primary features are rod–cone dystrophy, polydactyly which results in extra fingers and toes, obesity, cognitive impairment, hypogonadism in males, genital abnormalities, and renal anomalies [3]. The most common symptom of the disease is rod-cone dystrophy, a symptom in about 90% of patients [1]. This is where the light-sensing tissue at the back of the eye gradually deteriorates and causes the person to have worse and worse eyesight as they get older [1]. It eventually results in legal blindness at a young age for individuals with this disease [1]. Obesity occurs in about 72%-96% of patients depending on measurement criteria [3]. The most sever primary symptom is the renal, also known as kidney, anomalies and malformation because it eventually leads to end stage renal disease [4]. End stage renal disease can cause of morbidity of people with Bardet-Biedl Syndrome [4]. The frequency of this symptom is unknown do to its fairly recent association with Bardet-Biedl syndrome. Other symptoms associated with the disease include impaired speech, delayed development of motor skills, hypotonia which is low muscle tone, behavioral abnormalities, poor coordination and balance, diabetes, orodental abnormalities, and anosmia which is loss of smell [4]. Other conditions can also affect the heart and liver [1].
Bardet-Biedl syndrome can causes a large variety of symptoms. The symptoms themselves vary from individual to individual even if they are from the same family. The primary features are rod–cone dystrophy, polydactyly which results in extra fingers and toes, obesity, cognitive impairment, hypogonadism in males, genital abnormalities, and renal anomalies [3]. The most common symptom of the disease is rod-cone dystrophy, a symptom in about 90% of patients [1]. This is where the light-sensing tissue at the back of the eye gradually deteriorates and causes the person to have worse and worse eyesight as they get older [1]. It eventually results in legal blindness at a young age for individuals with this disease [1]. Obesity occurs in about 72%-96% of patients depending on measurement criteria [3]. The most sever primary symptom is the renal, also known as kidney, anomalies and malformation because it eventually leads to end stage renal disease [4]. End stage renal disease can cause of morbidity of people with Bardet-Biedl Syndrome [4]. The frequency of this symptom is unknown do to its fairly recent association with Bardet-Biedl syndrome. Other symptoms associated with the disease include impaired speech, delayed development of motor skills, hypotonia which is low muscle tone, behavioral abnormalities, poor coordination and balance, diabetes, orodental abnormalities, and anosmia which is loss of smell [4]. Other conditions can also affect the heart and liver [1].
How does a genetic mutation cause it?Bardet-Biedl syndrome is inherited in a autosomal recessive pattern meaning one must have a mutation in both genes to have the disease. A child that has Bardet-Biedl syndrome receives a mutated gene from each of his parents. One that has only one copy of the mutated gene typically does not have the symptoms of Bardet-Biedl syndrome but is a carrier for the disease[1].
This disease can result from a mutation in any one of 14 genes. However, the most common mutation that results in Bardet-Biedl syndrome is a mutation in the gene BBS1. A mutation in BBS1 accounts for about a quarter of cases [5]. The other 13 genes that when mutated result in this disease are ARL6, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, CEP290, MKKS, MKS1, TRIM32, TTC8 [6]. |
BBS1
Fig 2: BBS1 is located on Chromosome 11 and is indicated by the yellow arrow.
The full name of BBS1 is Bardet-Biedl Syndrome 1 (accession number NG_009093). The gene BBS1 is located on the long arm of chromosome 11 at position 13 [2]. The cytogenetic location is 11q 13 [2]. This gene is made up of 29,966 base pairs and is located from base pair 66,278,118 to 66,301,083 on chromosome 11. Over 30 different mutations in the BBS1 gene have been shown to cause Bardet-Biedl Syndrome [1].
BBS1 makes a protein in the body that is part of a complex that is critical in forming a cell structure called Cilia [2]. Cilia are found in many types of cells throughout the body which is why there is such a large range of symptoms with this disease. Cilia are microscopic, finger-like projections that are on the surface of cells and involved in cell movement and chemical signaling pathways [2]. They are also necessary for the perception of sensory input such as sight and smell [2]. Mutations in this gene cause the protein product to be altered when produced and therefore does not function properly. This results in defective cilia on cell surfaces. Due to the defects in these important cell structures, chemical signaling pathways are disrupted during development and lead to abnormalities of sensory perception which is believed to be the cause of all the symptoms of Bardet-Biedl Syndrome.
BBS1 makes a protein in the body that is part of a complex that is critical in forming a cell structure called Cilia [2]. Cilia are found in many types of cells throughout the body which is why there is such a large range of symptoms with this disease. Cilia are microscopic, finger-like projections that are on the surface of cells and involved in cell movement and chemical signaling pathways [2]. They are also necessary for the perception of sensory input such as sight and smell [2]. Mutations in this gene cause the protein product to be altered when produced and therefore does not function properly. This results in defective cilia on cell surfaces. Due to the defects in these important cell structures, chemical signaling pathways are disrupted during development and lead to abnormalities of sensory perception which is believed to be the cause of all the symptoms of Bardet-Biedl Syndrome.
What treatments are available?
Unfortunately, there is no cure for Bardet-Biedl syndrome. However, treatment is available for the different symptoms and individual has. Although nothing can reverse the symptoms, there are ways they are managed.
To access resources for families and patients, click the button on the right.
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~One Family's Success Story of their son with Bardet-Biedl Syndrome~
References:
[Banner Photo] "NDM-1" NDM-1. Retrieved 12 March 2013 from http://www.personal.psu.edu/czc5161/blogs/testing/references.html.
[1] "Bardet-Biedl Syndrome." Genetics Home Reference: Your Guide to Understanding Genetic Conditions. Retrieved 7 Feb 2013 from http://ghr.nlm.nih.gov/condition/bardet-biedl-syndrome
[2] "BBS1." Genetic Home Reference: Your Guide to Understanding Genetic Conditions. Retrieved 7 Feb 2013 from http://ghr.nlm.nih.gov/gene/BBS1
[3] "Exploring the molecular basis of Bardet-Biedl Syndrome." Human Molecular Genetics. Retrieved 7 Feb 2013 from http://hmg.oxfordjournals.org/content/10/20/2293/T1.expansion.html
[4] "Bardet-Biedl Syndrome." NCBI. Retrieved 7 Feb 2013 from http://www.ncbi.nlm.nih.gov/books/NBK1363/
[5] Ansley SJ, Badano JL, Blacque OE, Hill J, Hoskins BE, Leitch CC, Kim JC, Ross AJ, Elchers ER, Teslovich TM, Mah AK, Johnsen RC, Cavender JC, Lewis RA, Leroux MR, Beales PL, Katsanis N. Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome. Nature. 2003;425:628-33 [PubMed]
[6] "Related Genes." Genetics Home Reference: Your Guide to Understanding Genetic Conditions. Retrieved 7 Feb 2013 from http://ghr.nlm.nih.gov/condition/bardet-biedl-syndrome/show/Related+Gene(s)
[Banner Photo] "NDM-1" NDM-1. Retrieved 12 March 2013 from http://www.personal.psu.edu/czc5161/blogs/testing/references.html.
[1] "Bardet-Biedl Syndrome." Genetics Home Reference: Your Guide to Understanding Genetic Conditions. Retrieved 7 Feb 2013 from http://ghr.nlm.nih.gov/condition/bardet-biedl-syndrome
[2] "BBS1." Genetic Home Reference: Your Guide to Understanding Genetic Conditions. Retrieved 7 Feb 2013 from http://ghr.nlm.nih.gov/gene/BBS1
[3] "Exploring the molecular basis of Bardet-Biedl Syndrome." Human Molecular Genetics. Retrieved 7 Feb 2013 from http://hmg.oxfordjournals.org/content/10/20/2293/T1.expansion.html
[4] "Bardet-Biedl Syndrome." NCBI. Retrieved 7 Feb 2013 from http://www.ncbi.nlm.nih.gov/books/NBK1363/
[5] Ansley SJ, Badano JL, Blacque OE, Hill J, Hoskins BE, Leitch CC, Kim JC, Ross AJ, Elchers ER, Teslovich TM, Mah AK, Johnsen RC, Cavender JC, Lewis RA, Leroux MR, Beales PL, Katsanis N. Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome. Nature. 2003;425:628-33 [PubMed]
[6] "Related Genes." Genetics Home Reference: Your Guide to Understanding Genetic Conditions. Retrieved 7 Feb 2013 from http://ghr.nlm.nih.gov/condition/bardet-biedl-syndrome/show/Related+Gene(s)