Bardet-Biedl syndrome: Difference between revisions
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Two forms have been identified: | Two forms have been identified: | ||
* Bardet-Biedl syndrome 1 ({{Gene|BBS1}}) has no linkage to [[chromosome 16 (human)|chromosome 16]] | * Bardet-Biedl syndrome 1 ({{Gene|BBS1}}) has no linkage to [[chromosome 16 (human)|chromosome 16]] | ||
* Bardet-Biedl syndrome 2 ({{Gene|BBS2}}) is mapped to markers on chromosome 16. | * Bardet-Biedl syndrome 2 ({{Gene|BBS2}}) is mapped to markers on [[chromosome 16]]. | ||
== Major features == | ==Pathophysiology== | ||
* Eyes: | *The detailed biochemical mechanism that leads to BBS is still unclear. | ||
*The gene products encoded by these ''BBS'' genes, called BBS proteins, are located in the [[basal body]] and [[cilia]] of the [[Cell (biology)|cell]].<ref name="pmid14520415">{{cite journal | author = Ansley SJ, Badano JL, Blacque OE, Hill J, Hoskins BE, Leitch CC, Kim JC, Ross AJ, Eichers ER, Teslovich TM, Mah AK, Johnsen RC, Cavender JC, Lewis RA, Leroux MR, Beales PL, Katsanis N | title = Basal body dysfunction is a likely cause of pleiotropic Bardet–Biedl syndrome | journal = Nature | volume = 425 | issue = 6958 | pages = 628–33 | year = 2003 | month = October | pmid = 14520415 | doi = 10.1038/nature02030 | url = | issn = }}</ref> | |||
*Using the round worm ''[[Caenorhabditis elegans|C. elegans]]'' as a model system, biologists found that BBS proteins are involved in a process called [[Intraflagellar transport]] (IFT), a bi-directional transportation activity within the cilia along the long axis of the ciliary shaft that is essential for [[ciliogenesis]] and the maintenance of cilia.<ref>{{cite journal| author=Blacque OE, Reardon MJ, Li C, McCarthy J, Mahjoub MR, Ansley SJ, Badano JL, Mah AK, Beales PL, Davidson WS, Johnsen RC, Audeh M, Plasterk RH, Baillie DL, Katsanis N, Quarmby LM, Wicks SR, Leroux MR.|title=Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport | journal= Genes Dev. | volume=18 | pages=1630–42 | year= 2004 | pmid=15231740| doi=10.1101/gad.1194004| issue=13| pmc=443524}}</ref> Recent biochemical analysis of human BBS proteins revealed that BBS proteins are assembled into a multiple protein complex, called "BBSome". BBSome is proposed to be responsible for transporting intracellular vesicles to the base of the cilia and to play an important role in the ciliary function.{{cn|date=July 2012}} | |||
*Since abnormalities of cilia are known to be related to a wide range of disease symptoms including those commonly seen in BBS patients, it is now widely accepted that mutated BBS genes affect normal cilia functions, which, in turns, causes BBS.{{Citation needed|date=June 2008}} | |||
*Genes involved include:{{cn|date=July 2012}} | |||
**[[BBsome]]: [[BBS1]], [[BBS2]], [[BBS4]], [[BBS5]], [[BBS7]], [[TTC8]]/BBS8, [[BBS9]] | |||
**[[Chaperone (protein)|chaperone]]: [[BBS6]], [[BBS10]], [[BBS12]] | |||
**Other: [[ARL6]]/BBS3, [[TRIM32]]/BBS11 | |||
===Relation to other rare genetic disorders=== | |||
*Recent findings in genetic research have suggested that a large number of [[genetic disorder]]s, both [[Syndrome|genetic syndromes]] and [[Disease|genetic diseases]], that were not previously identified in the medical literature as related, may be, in fact, highly related in the [[genotype|genetypical]] root cause of the widely-varying, [[phenotype|phenotypically]]-observed [[Disorder (medicine)|disorders]]. | |||
*BBS is one such syndrome that has now been identified to be caused by defects in the [[Cell (biology)|cellular]] [[Cilium|ciliary structure]]. Thus, BBS is a [[ciliopathy]]. | |||
*Other known ciliopathies include [[primary ciliary dyskinesia]], [[polycystic kidney disease|polycystic kidney]] and [[polycystic liver disease|liver disease]], [[nephronophthisis]], [[Alstrom syndrome]], [[Meckel–Gruber syndrome]] and some forms of [[retinopathy|retinal degeneration]].<ref>{{cite journal |author=Badano JL, Mitsuma N, Beales PL, Katsanis N |title=The ciliopathies: an emerging class of human genetic disorders |journal=Annu Rev Genomics Hum Genet |volume=7 |issue= |pages=125–48 |year=2006 |pmid=16722803 |doi=10.1146/annurev.genom.7.080505.115610 |url=http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.genom.7.080505.115610}} | |||
</ref> | |||
==Major features== | |||
* Eyes: [[Retinitis pigmentosa]], [[poor visual acuity]], [[low vision]], and/or [[blindness]]. | |||
* Nose: Loss of, or reduced sense of, smell. ([[anosmia]]) | * Nose: Loss of, or reduced sense of, smell. ([[anosmia]]) | ||
* Hand and foot: [[Polydactyly]] or [[syndactyly]] (webbing of fingers and toes). | * Hand and foot: [[Polydactyly]] or [[syndactyly]] (webbing of fingers and toes). | ||
* Cardiovascular system: [[Organ hypertrophy|Hypertrophy]] of [[interventricular septum]] and [[left ventricle]] and | * Cardiovascular system: [[Organ hypertrophy|Hypertrophy]] of [[interventricular septum]] and [[left ventricle]] and [[dilated cardiomyopathy]]. | ||
* Gastrointestinal system: [[Fibrosis]]. | * Gastrointestinal system: [[Fibrosis]]. | ||
* Urogenital system: [[Hypogonadism]], [[renal failure]], [[urogenital sinuses]], [[ectopic urethra]], [[uterus duplex]], [[septate vagina]], and [[hypoplasia]] of the [[uterus]], [[ovaries]], and [[fallopian tubes]]. | * Urogenital system: [[Hypogonadism]], [[chronic renal failure]], [[urogenital sinuses]], [[ectopic urethra]], [[uterus duplex]], [[septate vagina]], and [[hypoplasia]] of the [[uterus]], [[ovaries]], and [[fallopian tubes]]. | ||
* Growth and development: Mental and growth [[retardation]]. | * Growth and development: Mental and growth [[retardation]]. | ||
* Behavior and performance: a wide variety of socialization and social interaction problems have been identified with BBS. Some refer to it as a kind of "mild-[[Autism]]." Many children who are later (explicitly and formally) diagnosed with the syndrome have gone through an extended period of time where school and medical professionals have struggled to find a name for the child's problems over several years. | * Behavior and performance: a wide variety of socialization and social interaction problems have been identified with BBS. Some refer to it as a kind of "mild-[[Autism]]." Many children who are later (explicitly and formally) diagnosed with the syndrome have gone through an extended period of time where school and medical professionals have struggled to find a name for the child's problems over several years. | ||
Revision as of 03:18, 9 August 2012
| Bardet-Biedl syndrome | |
| ICD-10 | Q87.8 |
|---|---|
| ICD-9 | 759.89 |
| OMIM | 209900 |
| DiseasesDB | 7286 |
| MeSH | D020788 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]
Synonyms and keywords: Laurence-Moon-Biedl syndrome; Laurence-Moon-Biedl-Bardet; LMBBS; LMBS
Overview
The Bardet-Biedl syndrome is a genetic disorder characterized mainly by obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, renal dysplasia and renal failure in some cases.[1]
Historical Perspective
The syndrome is named after Georges Bardet and Arthur Biedl.[2] The first known case was reported by Laurence and Moon in 1866 at the Ophthalmic Hospital in South London. Laurence-Moon-Biedl-Bardet syndrome are no longer considered as valid terms in that patients of Laurence and Moon had paraplegia but no polydactyly and obesity which are the key elements of the Bardet-Biedl the syndrome. Laurence-Moon syndrome is usually considered a separate entity. However, some recent research suggests that the two conditions may not be distinct.[3]
Classification
Two forms have been identified:
- Bardet-Biedl syndrome 1 (BBS1) has no linkage to chromosome 16
- Bardet-Biedl syndrome 2 (BBS2) is mapped to markers on chromosome 16.
Pathophysiology
- The detailed biochemical mechanism that leads to BBS is still unclear.
- The gene products encoded by these BBS genes, called BBS proteins, are located in the basal body and cilia of the cell.[4]
- Using the round worm C. elegans as a model system, biologists found that BBS proteins are involved in a process called Intraflagellar transport (IFT), a bi-directional transportation activity within the cilia along the long axis of the ciliary shaft that is essential for ciliogenesis and the maintenance of cilia.[5] Recent biochemical analysis of human BBS proteins revealed that BBS proteins are assembled into a multiple protein complex, called "BBSome". BBSome is proposed to be responsible for transporting intracellular vesicles to the base of the cilia and to play an important role in the ciliary function.[citation needed]
- Since abnormalities of cilia are known to be related to a wide range of disease symptoms including those commonly seen in BBS patients, it is now widely accepted that mutated BBS genes affect normal cilia functions, which, in turns, causes BBS.[citation needed]
- Genes involved include:[citation needed]
Relation to other rare genetic disorders
- Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely-varying, phenotypically-observed disorders.
- BBS is one such syndrome that has now been identified to be caused by defects in the cellular ciliary structure. Thus, BBS is a ciliopathy.
- Other known ciliopathies include primary ciliary dyskinesia, polycystic kidney and liver disease, nephronophthisis, Alstrom syndrome, Meckel–Gruber syndrome and some forms of retinal degeneration.[6]
Major features
- Eyes: Retinitis pigmentosa, poor visual acuity, low vision, and/or blindness.
- Nose: Loss of, or reduced sense of, smell. (anosmia)
- Hand and foot: Polydactyly or syndactyly (webbing of fingers and toes).
- Cardiovascular system: Hypertrophy of interventricular septum and left ventricle and dilated cardiomyopathy.
- Gastrointestinal system: Fibrosis.
- Urogenital system: Hypogonadism, chronic renal failure, urogenital sinuses, ectopic urethra, uterus duplex, septate vagina, and hypoplasia of the uterus, ovaries, and fallopian tubes.
- Growth and development: Mental and growth retardation.
- Behavior and performance: a wide variety of socialization and social interaction problems have been identified with BBS. Some refer to it as a kind of "mild-Autism." Many children who are later (explicitly and formally) diagnosed with the syndrome have gone through an extended period of time where school and medical professionals have struggled to find a name for the child's problems over several years.
- Heredity: The syndrome is familial and is transmitted as an autosomal recessive trait. chromosome 3 locus appears to be linked to polydactyly of all four limbs, whereas chromosome 15 is associated with early-onset morbid obesity and is mostly confined to the hands, and chromosome 16 represents the "leanest" form.
- Additional features: Obesity.
Cause
The detail biochemical mechanism that leads to BBS is still unclear. Recently, eight genes (BBS1 to BBS8) that are responsible for the disease when mutated have been cloned, and most of the gene products encoded by these BBS genes are located in the basal body and cilia of the cell. It has been postulated that these BBS gene products might involve in the cell signaling pathway in the cilia, and these signaling systems play an essential role in the normal development so that a malfunction in these systems causes the diverse pathological effects of the Syndrome.
In addition to so-called "signaling' along the cilia, it appears that Intraflagellar transport (IFT) of proteins along the cilia are essential for the formation and maintenance of healthy cells. In particular, abnormalities in retinal cilia are hypothesized to be related to the retinal dystrophy which is common in BBS patients.
June 2006 Conference
- The LMBBS Association Family Meeting for non-medical-professionals was held in Houston, Texas, June 16-17, 2006.
- The conference was sponsored by a steering committee of BBS folk and parents/grandparents of children with BBS. It was directed to a lay audience.
- A primary purpose of the conference was to present the latest medical research results in an accessible fashion. This included one morning of presentations by leading BBS genetic researchers Dr. Richard Lewis (Baylor Medical Center, Houston) and Dr. Nicholas Katsanis (Johns Hopkins University, Baltimore, Maryland). Several additional doctors presented accessible information on growth and weight management; kidney issues; obesity & Syndrome X; pediatric bariatric surgery; and speech pathology & therapy.
- Location: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas.
- For additional information about the meeting, click here.
References
- ↑ Beales P, Elcioglu N, Woolf A, Parker D, Flinter F (1999). "New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey". J. Med. Genet. 36 (6): 437–46. PMID 10874630.
- ↑ Template:WhoNamedIt
- ↑ Moore S, Green J, Fan Y; et al. (2005). "Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: a 22-year prospective, population-based, cohort study". Am. J. Med. Genet. A. 132 (4): 352–60. PMID 15637713.
- ↑ Ansley SJ, Badano JL, Blacque OE, Hill J, Hoskins BE, Leitch CC, Kim JC, Ross AJ, Eichers ER, Teslovich TM, Mah AK, Johnsen RC, Cavender JC, Lewis RA, Leroux MR, Beales PL, Katsanis N (2003). "Basal body dysfunction is a likely cause of pleiotropic Bardet–Biedl syndrome". Nature. 425 (6958): 628–33. doi:10.1038/nature02030. PMID 14520415. Unknown parameter
|month=ignored (help) - ↑ Blacque OE, Reardon MJ, Li C, McCarthy J, Mahjoub MR, Ansley SJ, Badano JL, Mah AK, Beales PL, Davidson WS, Johnsen RC, Audeh M, Plasterk RH, Baillie DL, Katsanis N, Quarmby LM, Wicks SR, Leroux MR. (2004). "Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport". Genes Dev. 18 (13): 1630–42. doi:10.1101/gad.1194004. PMC 443524. PMID 15231740.
- ↑ Badano JL, Mitsuma N, Beales PL, Katsanis N (2006). "The ciliopathies: an emerging class of human genetic disorders". Annu Rev Genomics Hum Genet. 7: 125–48. doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803.
External links
- Laurence Moon Bardet Biedl Society (UK-based)
- LMBBS Association (US-based; newly formed in June at the Houston 2006 BBS conference)
- The Importance of Being Cilia Accessible article at Howard Hughes Medical Institute on the importance and extensive use of cilia and basal bodies in many organ systems of human physiology. Includes multiple specific mentions of BBS.
- BBS and loss of the sense of smell at Johns Hopkins University
- Overview at United States National Library of Medicine
- Foundation Fighting Blindness
- Bardet-Biedl Syndrome Association francaise (France-based; in French language) Syndrome de Bardet-Biedl (BBS)
Template:Phakomatoses and other congenital malformations not elsewhere classified
da:Moon-Bardet-Biedl syndrom de:Laurence-Moon-Biedl-Bardet-Syndrom nl:Syndroom van Laurence-Moon-Bardet-Biedl fi:Bardet-Biedlin oireyhtymä
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- Genetic disorders
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