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Leslie G. Biesecker - One of the best experts on this subject based on the ideXlab platform.
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genitourinary malformations as a feature of the pallister hall Syndrome
Clinical Dysmorphology, 2006Co-Authors: Emma Mccann, Alan Fryer, Ross J Craigie, Colin Baillie, Muhammed E Baath, Andrew Selby, Leslie G. BieseckerAbstract:Pallister-Hall and McKusick-Kaufman Syndromes are developmental disorders with well defined phenotypes, distinct loci and different patterns of inheritance. The clinical features can overlap and may cause diagnostic difficulty, particularly if complex genitourinary malformations are present. A case is presented with features of both Syndromes but in which a GLI3 mutation has been identified. A literature review of similar cases is presented and it is proposed that these cases probably represent the Pallister-Hall Syndrome. A detailed abdominal and perineal examination should be considered in all female patients with the Pallister-Hall Syndrome, looking for associated genitourinary anomalies. Conversely, all girls with features suggestive of McKusick-Kaufman Syndrome require neuroimaging to look for features of the Pallister-Hall Syndrome. The correct diagnosis is important so that the patient and the family may receive appropriate management. It also allows provision for an accurate recurrence risk.
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phenotypic overlap of McKusick Kaufman Syndrome with bardet biedl Syndrome a literature review
American Journal of Medical Genetics, 2000Co-Authors: Anne Slavotinek, Leslie G. BieseckerAbstract:Hydrometrocolpos (HMC) and post-axial polydactyly (PAP) are common to both McKusick-Kaufman Syndrome (MKS) and Bardet-Biedl Syndrome (BBS). We review reported cases of MKS and BBS presenting with HMC and PAP early in life to determine if there are clinical features that allow discrimination between the two Syndromes as the primary features of retinitis pigmentosa, obesity, learning disability in BBS are age-dependent. We did not find any phenotypic features that allowed reliable differentiation between the two Syndromes in the neonatal period. However, uterine, ovarian, and fallopian tube anomalies are more common in BBS patients, and it may be that these clinical features prove to be useful discriminating features. We conclude that sporadic female infants with HMC and PAP cannot be diagnosed with MKS until at least age 5 years and that monitoring for the complications of BBS should be performed in these patients.
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mutation of a gene encoding a putative chaperonin causes McKusick Kaufman Syndrome
Nature Genetics, 2000Co-Authors: Deborah L. Stone, Anne Slavotinek, Gerard G Bouffard, Sharmila Banerjeebasu, Andreas D Baxevanis, Mason Barr, Leslie G. BieseckerAbstract:McKusick-Kaufman Syndrome (MKKS, MIM 236700) is a human developmental anomaly Syndrome comprising hydrometrocolpos (HMC), postaxial polydactyly (PAP) and congenital heart disease1,2 (CHD). MKKS has been mapped in the Old Order Amish population to 20p12, between D20S162 and D20S894 (ref. 3). Here we describe the identification of a gene mutated in MKKS. We analysed the approximately 450-kb candidate region by sample sequencing, which revealed the presence of several known genes and EST clusters. We evaluated candidate transcripts by northern-blot analysis of adult and fetal tissues. We selected one transcript with widespread expression, MKKS, for analysis in a patient from the Amish pedigree and a sporadic, non-Amish case. The Old Order Amish patient was found to be homozygous for an allele that had two missense substitutions and the non-Amish patient was a compound heterozygote for a frameshift mutation predicting premature protein truncation and a distinct missense mutation. The MKKS predicted protein shows amino acid similarity to the chaperonin family of proteins, suggesting a role for protein processing in limb, cardiac and reproductive system development. We believe that this is the first description of a human disorder caused by mutations affecting a putative chaperonin molecule.
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Genetic and physical mapping of the McKusick–Kaufman Syndrome
1997Co-Authors: Deborah L. Stone, Richa Agarwala, Ro A. Schäffer, James L. Weber, David Vaske, Takaya Oda, Clair A. Francomano, Leslie G. BieseckerAbstract:McKusick–Kaufman Syndrome is a human developmental anomaly Syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos. This Syndrome is diagnosed most frequently in the Old Order Amish population and is inherited in an autosomal recessive pattern with reduced penetrance and variable expressivity. Homozygosity mapping and linkage analyses were conducted using two pedigrees derived from a larger pedigree published in 1978. The PedHunter software query system was used on the Amish Genealogy Database to correct the previous pedigree, derive a minimal pedigree connecting those affected sibships that are in the database and determine the most recent common ancestors of the affected persons. Whole genome short tandem repeat polymorphism (STRP) screening showed homozygosity in 20p12, between D20S162 and D20S894, an area that includes the Alagille Syndrome critical region. The peak two-point LOD score was 3.33, and the peak three-point LOD score was 5.21. The physical map of this region has been defined, and additional polymorphic markers have been isolated. The region includes several genes and expressed sequence tags (ESTs), including the jagged1 gene that recently has been shown to be haploinsufficient in the Alagille Syndrome. Sequencing of jagged1 in two unrelated individuals affected with McKusick–Kaufman Syndrome has not revealed any disease-causing mutations
Vera Coelho Teixeira - One of the best experts on this subject based on the ideXlab platform.
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Anestesia em paciente portadora de síndrome de McKusick-Kaufman: relato de caso Anestesia en paciente portadora de síndrome de McKusick-Kaufman: relato de caso Anesthesia in McKusick-Kaufman Syndrome patient: case report
Sociedade Brasileira de Anestesiologia, 2004Co-Authors: Adriano Bechara De Souza Hobaika, Ziltomar Donizetti Borges, Vera Coelho TeixeiraAbstract:JUSTIFICATIVA E OBJETIVOS: A síndrome de McKusick-Kaufman é uma doença rara, caracterizada tipicamente por hidrometrocolpos, polidactilia e defeitos cardíacos congênitos. Pacientes portadores desta doença podem ser submetidos a diversos procedimentos cirúrgicos durante a sua vida e o anestesiologista deve estar preparado para possíveis alterações. O objetivo deste artigo é relatar a conduta anestésica adotada em uma paciente portadora desta síndrome. RELATO DO CASO: Paciente do sexo feminino de 11 anos, 37 kg, portadora da síndrome de McKusick-Kaufman, insuficiência renal crônica, encefalopatia hipertensiva e asma grave submetida à retirada de cateter peritoneal infectado e confecção de fístula arteriovenosa. História pregressa de intubação prolongada. A anestesia foi induzida com alfentanil (1 mg), propofol (50 mg) e atracúrio (25 mg) e mantida com sevoflurano (2% a 4%) e doses fracionadas de alfentanil. A traquéia foi intubada sem complicações e a extubação foi realizada na sala de cirurgia após o retorno satisfatório da função neuromuscular. CONCLUSÕES: Apesar de a síndrome de McKusick-Kaufman tratar-se de uma associação variável de defeitos congênitos, alguns cuidados anestésicos comuns podem ser definidos. Este caso apresentou fatores complicadores da anestesia e a indução com propofol e alfentanil e a manutenção com sevoflurano proporcionaram à paciente uma anestesia com mínimas repercussões ventilatórias e hemodinâmicas.JUSTIFICATIVA Y OBJETIVOS: La síndrome de McKusick-Kaufman es una dolencia rara, caracterizada típicamente por hidrometrocolpos, polidactilia y defectos cardiacos congénitos. Pacientes portadores de esta enfermedad pueden ser sometidos a varios procedimientos cirúrgicos durante su vida y el anestesiologista debe estar preparado para posibles alteraciones. El objetivo de este artículo es relatar la conducta anestésica adoptada en una paciente portadora de este síndrome. RELATO DEL CASO: Paciente del sexo femenino de 11 años, 37 kg, portadora del síndrome de McKusick-Kaufman, insuficiencia renal crónica, encefalopatia hipertensiva y asma grave sometida a la retirada de catéter peritoneal infectado y a una confección de fístula arteriovenosa. Historia anterior de intubación prolongada. La anestesia fue inducida con alfentanil (1 mg), propofol (50 mg) y atracúrio (25 mg) y mantenida con sevoflurano (2% a 4%) y dosis fraccionadas de alfentanil. La tráquea fue intubada sin complicaciones y la extubación fue realizada en la sala de cirugía después del retorno satisfactorio de la función neuromuscular. CONCLUSIONES: A pesar que el síndrome de McKusick-Kaufman se trate de una asociación variable de defectos congénitos, algunas atenciones anestésicas comunes pueden ser definidas. Este caso presentó factores complicadores de la anestesia y la inducción con propofol y alfentanil y el mantenimiento con sevoflurano proporcionaron a la paciente una anestesia con mínimas repercusiones ventilatorias y hemodinámicas.BACKGROUND AND OBJECTIVES: McKusick-Kaufman Syndrome is an uncommon disease, typically characterized by hydrometrocolpos, polydactyly and congenital heart defects. These patients are often submitted to different surgical procedures throughout their lives and the anesthesiologist must be prepared to deal with possible complications. This article aimed at reporting the anesthetic management adopted for a patient with this Syndrome. CASE REPORT: A 11-year-old, 37 kg, female with McKusick-Kaufman Syndrome, chronic renal failure, hypertensive encephalopathy and severe asthma was scheduled for surgical arterial-venous fistula preparation and removal of infected peritoneal dialysis catheter. Previous prolonged tracheal intubation was reported. Anesthesia was induced with alfentanil (1 mg), propofol (50 mg) and atracurium (25 mg) and was maintained with inhalational sevoflurane (2% to 4%) and intermittent IV alfentanil doses. Trachea was intubated without intercurrences and extubation was performed in the operating room after satisfactory neuromuscular function recovery. CONCLUSIONS: Although McKusick-Kaufman Syndrome is a variable association of congenital defects, some standard anesthetic cares may be defined. This specific case presented complicating factors for anesthesia, and induction with propofol and alfentanil and maintenance with sevoflurane have provided the patient a perioperative period with minimal ventilatory and hemodynamic repercussions
Teixeira, Vera Coelho - One of the best experts on this subject based on the ideXlab platform.
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Anestesia en paciente portadora de síndrome de McKusick-Kaufman: relato de caso
Sociedade Brasileira de Anestesiologia, 2004Co-Authors: Hobaika, Adriano Bechara De Souza, Borges, Ziltomar Donizetti, Teixeira, Vera CoelhoAbstract:JUSTIFICATIVA E OBJETIVOS: A síndrome de McKusick-Kaufman é uma doença rara, caracterizada tipicamente por hidrometrocolpos, polidactilia e defeitos cardíacos congênitos. Pacientes portadores desta doença podem ser submetidos a diversos procedimentos cirúrgicos durante a sua vida e o anestesiologista deve estar preparado para possíveis alterações. O objetivo deste artigo é relatar a conduta anestésica adotada em uma paciente portadora desta síndrome. RELATO DO CASO: Paciente do sexo feminino de 11 anos, 37 kg, portadora da síndrome de McKusick-Kaufman, insuficiência renal crônica, encefalopatia hipertensiva e asma grave submetida à retirada de cateter peritoneal infectado e confecção de fístula arteriovenosa. História pregressa de intubação prolongada. A anestesia foi induzida com alfentanil (1 mg), propofol (50 mg) e atracúrio (25 mg) e mantida com sevoflurano (2% a 4%) e doses fracionadas de alfentanil. A traquéia foi intubada sem complicações e a extubação foi realizada na sala de cirurgia após o retorno satisfatório da função neuromuscular. CONCLUSÕES: Apesar de a síndrome de McKusick-Kaufman tratar-se de uma associação variável de defeitos congênitos, alguns cuidados anestésicos comuns podem ser definidos. Este caso apresentou fatores complicadores da anestesia e a indução com propofol e alfentanil e a manutenção com sevoflurano proporcionaram à paciente uma anestesia com mínimas repercussões ventilatórias e hemodinâmicas.BACKGROUND AND OBJECTIVES: McKusick-Kaufman Syndrome is an uncommon disease, typically characterized by hydrometrocolpos, polydactyly and congenital heart defects. These patients are often submitted to different surgical procedures throughout their lives and the anesthesiologist must be prepared to deal with possible complications. This article aimed at reporting the anesthetic management adopted for a patient with this Syndrome. CASE REPORT: A 11-year-old, 37 kg, female with McKusick-Kaufman Syndrome, chronic renal failure, hypertensive encephalopathy and severe asthma was scheduled for surgical arterial-venous fistula preparation and removal of infected peritoneal dialysis catheter. Previous prolonged tracheal intubation was reported. Anesthesia was induced with alfentanil (1 mg), propofol (50 mg) and atracurium (25 mg) and was maintained with inhalational sevoflurane (2% to 4%) and intermittent IV alfentanil doses. Trachea was intubated without intercurrences and extubation was performed in the operating room after satisfactory neuromuscular function recovery. CONCLUSIONS: Although McKusick-Kaufman Syndrome is a variable association of congenital defects, some standard anesthetic cares may be defined. This specific case presented complicating factors for anesthesia, and induction with propofol and alfentanil and maintenance with sevoflurane have provided the patient a perioperative period with minimal ventilatory and hemodynamic repercussions.JUSTIFICATIVA Y OBJETIVOS: La síndrome de McKusick-Kaufman es una dolencia rara, caracterizada típicamente por hidrometrocolpos, polidactilia y defectos cardiacos congénitos. Pacientes portadores de esta enfermedad pueden ser sometidos a varios procedimientos cirúrgicos durante su vida y el anestesiologista debe estar preparado para posibles alteraciones. El objetivo de este artículo es relatar la conducta anestésica adoptada en una paciente portadora de este síndrome. RELATO DEL CASO: Paciente del sexo femenino de 11 años, 37 kg, portadora del síndrome de McKusick-Kaufman, insuficiencia renal crónica, encefalopatia hipertensiva y asma grave sometida a la retirada de catéter peritoneal infectado y a una confección de fístula arteriovenosa. Historia anterior de intubación prolongada. La anestesia fue inducida con alfentanil (1 mg), propofol (50 mg) y atracúrio (25 mg) y mantenida con sevoflurano (2% a 4%) y dosis fraccionadas de alfentanil. La tráquea fue intubada sin complicaciones y la extubación fue realizada en la sala de cirugía después del retorno satisfactorio de la función neuromuscular. CONCLUSIONES: A pesar que el síndrome de McKusick-Kaufman se trate de una asociación variable de defectos congénitos, algunas atenciones anestésicas comunes pueden ser definidas. Este caso presentó factores complicadores de la anestesia y la inducción con propofol y alfentanil y el mantenimiento con sevoflurano proporcionaron a la paciente una anestesia con mínimas repercusiones ventilatorias y hemodinámicas
Charles Searby - One of the best experts on this subject based on the ideXlab platform.
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Nuclear/cytoplasmic transport defects in BBS6 underlie congenital heart disease through perturbation of a chromatin remodeling protein
2017Co-Authors: Charles Anthony Scott, Qihong Zhang, Charles Searby, Val C Sheffield, Lisa M Baye, Xitiz Chamling, Autumn N. Marsden, Michael R. Rebagliati, Diane C SlusarskiAbstract:Mutations in BBS6 cause two clinically distinct Syndromes, Bardet-Biedl Syndrome (BBS), a Syndrome caused by defects in cilia transport and function, as well as McKusick-Kaufman Syndrome, a genetic disorder characterized by congenital heart defects. Congenital heart defects are rare in BBS, and McKusick-Kaufman Syndrome patients do not develop retinitis pigmentosa. Therefore, the McKusick-Kaufman Syndrome allele may highlight cellular functions of BBS6 distinct from the presently understood functions in the cilia. In support, we find that the McKusick-Kaufman Syndrome disease-associated allele, BBS6H84Y; A242S, maintains cilia function. We demonstrate that BBS6 is actively transported between the cytoplasm and nucleus, and that BBS6H84Y; A242S, is defective in this transport. We developed a transgenic zebrafish with inducible bbs6 to identify novel binding partners of BBS6, and we find interaction with the SWI/SNF chromatin remodeling protein Smarcc1a (SMARCC1 in humans). We demonstrate that through this interaction, BBS6 modulates the sub-cellular localization of SMARCC1 and find, by transcriptional profiling, similar transcriptional changes following smarcc1a and bbs6 manipulation. Our work identifies a new function for BBS6 in nuclear-cytoplasmic transport, and provides insight into the disease mechanism underlying the congenital heart defects in McKusick-Kaufman Syndrome patients.
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mkks null mice have a phenotype resembling bardet biedl Syndrome
Human Molecular Genetics, 2005Co-Authors: Melissa A. Fath, Charles Searby, Darryl Y Nishimura, Kamal Rahmouni, Marwan K Tayeh, Robert F Mullins, Michael P. Andrews, Roger E Davis, Jun Wei, Baoli YangAbstract:McKusick-Kaufman Syndrome (MKS) is an autosomal recessive disorder characterized by post-axial polydactyly, congenital heart defects and hydrometrocolpos, a congenital structural abnormality of female genitalia. Mutations in the MKKS gene have also been shown to cause some cases of Bardet-Biedl Syndrome (BBS) which is characterized by obesity, pigmentary retinopathy, polydactyly, renal abnormalities and hypogenitalism with secondary features of hypertension and diabetes. Although there is overlap in clinical features between MKS and BBS, MKS patients are not obese and do not develop retinopathy or have learning disabilities. To further explore the pathophysiology of BBS and the related disorder MKS, we have developed an Mkks -/- mouse model. This model shows that the absence of Mkks leads to retinal degeneration through apoptosis, failure of spermatozoa flagella formation, elevated blood pressure and obesity. The obesity is associated with hyperphagia and decreased activity. In addition, neurological screening reveals deficits in olfaction and social dominance. The mice do not have polydactyly or vaginal abnormalities. The phenotype of the Mkks -/- mice closely resembles the phenotype of other mouse models of BBS (Bbs2 -/- and Bbs4 -/- ). These observations suggest that the complete absence of MKKS leads to BBS while the MKS phenotype is likely to be due to specific mutations.
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Identification of the gene (BBS1) most commonly involved in Bardet-Biedl Syndrome, a complex human obesity Syndrome.
Nature genetics, 2002Co-Authors: Kirk Mykytyn, Charles Searby, John S Beck, Darryl Y Nishimura, Mythreyi Shastri, Hsan Jan Yen, Terry A. Braun, Luan M. Streb, Alberto S. Cornier, Gerald F. CoxAbstract:Bardet-Biedl Syndrome (BBS, OMIM 209900) is a genetic disorder with the primary features of obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation and hypogenitalism1,2,3,4. Individuals with BBS are also at increased risk for diabetes mellitus, hypertension and congenital heart disease4,5,6. What was once thought to be a homogeneous autosomal recessive disorder is now known to map to at least six loci: 11q13 (BBS1), 16q21 (BBS2), 3p13–p12 (BBS3), 15q22.3–q23 (BBS4), 2q31 (BBS5) and 20p12 (BBS6)7,8,9,10,11,12,13. There has been considerable interest in identifying the genes that underlie BBS, because some components of the phenotype are common. Cases of BBS mapping ro BBS6 are caused by mutations in MKKS12,13; mutations in this gene also cause McKusick-Kaufman Syndrome (hydrometrocolpos, post-axial polydactyly and congenital heart defects)14,15. In addition, we recently used positional cloning to identify the genes underlying BBS2 (ref. 16) and BBS4 (ref. 17). The BBS6 protein has similarity to a Thermoplasma acidophilum chaperonin15, whereas BBS2 and BBS4 have no significant similarity to chaperonins. It has recently been suggested that three mutated alleles (two at one locus, and a third at a second locus) may be required for manifestation of BBS (triallelic inheritance)18. Here we report the identification of the gene BBS1 and show that a missense mutation of this gene is a frequent cause of BBS. In addition, we provide data showing that this common mutation is not involved in triallelic inheritance.
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identification of the gene that when mutated causes the human obesity Syndrome bbs4
Nature Genetics, 2001Co-Authors: Kirk Mykytyn, Charles Searby, Rivka Carmi, Mythreyi Shastri, Terry A. Braun, Gretel Beck, Neena B Haider, Alan F Wright, Alessandro IannacconeAbstract:Bardet–Biedl Syndrome (BBS, MIM 209900) is a heterogeneous autosomal recessive disorder characterized by obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism1,2,3,4. The disorder is also associated with diabetes mellitus, hypertension, and congenital heart disease4,5,6. Six distinct BBS loci map to 11q13 (BBS1), 16q21 (BBS2), 3p13–p12 (BBS3), 15q22.3–q23 (BBS4), 2q31 (BBS5), and 20p12 (BBS6)7,8,9,10,11,12,13. Although BBS is rare in the general population (<1/100,000), there is considerable interest in identifying the genes causing BBS because components of the phenotype, such as obesity and diabetes, are common. We and others have demonstrated that BBS6 is caused by mutations in the gene MKKS (refs. 12,13), mutation of which also causes McKusick–Kaufman Syndrome (hydrometrocolpos, post-axial polydactyly, and congenital heart defects)14,15. MKKS has sequence homology to the alpha subunit of a prokaryotic chaperonin in the thermosome Thermoplasma acidophilum15. We recently identified a novel gene that causes BBS216. The BBS2 protein has no significant similarity to other chaperonins or known proteins. Here we report the positional cloning and identification of mutations in BBS patients in a novel gene designated BBS4.
Terry A. Braun - One of the best experts on this subject based on the ideXlab platform.
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Identification of the gene (BBS1) most commonly involved in Bardet-Biedl Syndrome, a complex human obesity Syndrome.
Nature genetics, 2002Co-Authors: Kirk Mykytyn, Charles Searby, John S Beck, Darryl Y Nishimura, Mythreyi Shastri, Hsan Jan Yen, Terry A. Braun, Luan M. Streb, Alberto S. Cornier, Gerald F. CoxAbstract:Bardet-Biedl Syndrome (BBS, OMIM 209900) is a genetic disorder with the primary features of obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation and hypogenitalism1,2,3,4. Individuals with BBS are also at increased risk for diabetes mellitus, hypertension and congenital heart disease4,5,6. What was once thought to be a homogeneous autosomal recessive disorder is now known to map to at least six loci: 11q13 (BBS1), 16q21 (BBS2), 3p13–p12 (BBS3), 15q22.3–q23 (BBS4), 2q31 (BBS5) and 20p12 (BBS6)7,8,9,10,11,12,13. There has been considerable interest in identifying the genes that underlie BBS, because some components of the phenotype are common. Cases of BBS mapping ro BBS6 are caused by mutations in MKKS12,13; mutations in this gene also cause McKusick-Kaufman Syndrome (hydrometrocolpos, post-axial polydactyly and congenital heart defects)14,15. In addition, we recently used positional cloning to identify the genes underlying BBS2 (ref. 16) and BBS4 (ref. 17). The BBS6 protein has similarity to a Thermoplasma acidophilum chaperonin15, whereas BBS2 and BBS4 have no significant similarity to chaperonins. It has recently been suggested that three mutated alleles (two at one locus, and a third at a second locus) may be required for manifestation of BBS (triallelic inheritance)18. Here we report the identification of the gene BBS1 and show that a missense mutation of this gene is a frequent cause of BBS. In addition, we provide data showing that this common mutation is not involved in triallelic inheritance.
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identification of the gene that when mutated causes the human obesity Syndrome bbs4
Nature Genetics, 2001Co-Authors: Kirk Mykytyn, Charles Searby, Rivka Carmi, Mythreyi Shastri, Terry A. Braun, Gretel Beck, Neena B Haider, Alan F Wright, Alessandro IannacconeAbstract:Bardet–Biedl Syndrome (BBS, MIM 209900) is a heterogeneous autosomal recessive disorder characterized by obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism1,2,3,4. The disorder is also associated with diabetes mellitus, hypertension, and congenital heart disease4,5,6. Six distinct BBS loci map to 11q13 (BBS1), 16q21 (BBS2), 3p13–p12 (BBS3), 15q22.3–q23 (BBS4), 2q31 (BBS5), and 20p12 (BBS6)7,8,9,10,11,12,13. Although BBS is rare in the general population (<1/100,000), there is considerable interest in identifying the genes causing BBS because components of the phenotype, such as obesity and diabetes, are common. We and others have demonstrated that BBS6 is caused by mutations in the gene MKKS (refs. 12,13), mutation of which also causes McKusick–Kaufman Syndrome (hydrometrocolpos, post-axial polydactyly, and congenital heart defects)14,15. MKKS has sequence homology to the alpha subunit of a prokaryotic chaperonin in the thermosome Thermoplasma acidophilum15. We recently identified a novel gene that causes BBS216. The BBS2 protein has no significant similarity to other chaperonins or known proteins. Here we report the positional cloning and identification of mutations in BBS patients in a novel gene designated BBS4.