Journal ArticleDOI
Identification of the gene that, when mutated, causes the human obesity syndrome BBS4
Kirk Mykytyn,Terry A. Braun,Terry A. Braun,Rivka Carmi,Neena B. Haider,Charles Searby,Mythreyi Shastri,Gretel Beck,Alan F. Wright,Alessandro Iannaccone,Khalil Elbedour,Ruth Riise,Alfonso Baldi,Annick Raas-Rothschild,Susan W. Gorman,David Duhl,Samuel G. Jacobson,Thomas L. Casavant,Edwin M. Stone,Val C. Sheffield +19 more
TLDR
The positional cloning and identification of mutations in BBS patients in a novel gene designated BBS4 is reported, which has no significant similarity to other chaperonins or known proteins.Abstract:
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.read more
Citations
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Journal ArticleDOI
Novel Compound Heterozygous BBS2 and Homozygous MKKS Variants Detected in Chinese Families with Bardet-Biedl Syndrome.
TL;DR: Wang et al. as discussed by the authors reported the genetic causes and clinical manifestations in two Chinese families with BBS, and two compound heterozygous variants c.235T > G (p.T79P) and c.534 + 1G > T were detected in the BBS2 gene in family A, and known homozygous variant c.748G > A(p.G250R) was detected in family B. Sanger sequencing was used to verify the variants and to perform a segregation analysis.
Proceedings ArticleDOI
Comparative genome annotation for mapping, prediction and discovery of genes
C. Kappen,J.M. Salbaum +1 more
TL;DR: This work presents its framework for data interpretation and demonstrates that unfinished sequences can be used to assemble maps of complex genomic loci with good accuracy and provides criteria for the implementation of automated genome annotation strategies.
Ciliopathies : molecular and genetic basis for Ahi1 function in retinal degeneration
TL;DR: Analysis of retina from Ahi1-/- mice revealed a phenotype consistent with the retinal involvement frequently observed in patients with deleterious A HI1 mutations, and an allele of AHI1 modifies the relative risk of retinal degeneration greater than 7 fold within a cohort of nephronopthisis patients.
Journal ArticleDOI
Combined CNV, haplotyping and whole exome sequencing enable identification of two distinct novel EYS mutations causing RP in a single inbred tribe.
Ohad Wormser,Libe Gradstein,Einat Kadar,Yuval Yogev,Yonatan Perez,Elena Mashkit,Khalil Elbedour,Max Drabkin,Barak Markus,Rotem Kadir,Daniel Halperin,Soltan Khalaila,Jaime Levy,Tova Lifshitz,Esther Manor,Ohad S. Birk +15 more
TL;DR: The findings of two distinct mutations in the same gene in a single inbred kindred, identified only through combined WES and microarray CNV analysis, highlight the limitations of either CNV or WES alone, as the heterozygous deletion had normal WES read‐depth values.
Journal ArticleDOI
Gene therapy rescues olfactory perception in a clinically relevant ciliopathy model of Bardet-Biedl syndrome.
Chao Xie,Julien C Habif,Cedric Uytingco,Kirill Ukhanov,Lian Zhang,Carlos de Celis,Val C. Sheffield,Jeffrey R. Martens +7 more
TL;DR: In this paper, the authors investigated the impact of the BBS1M390R mutation on the olfactory system and tested the potential of viral-mediated, wild-type gene replacement therapy to rescue smell loss.
References
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Journal ArticleDOI
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TL;DR: A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score.
Journal ArticleDOI
Fast and sensitive silver staining of DNA in polyacrylamide gels
TL;DR: The photochemically derived silver stain of nucleic acids in polyacrylamide gels originally described by Merril et al. was modified to reduce unspecific background staining and increase sensitivity and this improved staining procedure is applied for the routine analysis of complex DNA profiles generated by DNA amplification fingerprinting (DAF).
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Gregory L. Blatch,Michael Lässle +1 more
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Journal ArticleDOI
The cardinal manifestations of Bardet-Biedl syndrome, a form of Laurence-Moon-Biedl syndrome.
Jane Green,Patrick S. Parfrey,John D. Harnett,Nadir R. Farid,Benvon C. Cramer,Gordon J. Johnson,Olga Heath,P J McManamon,Elizabeth O'Leary,William Pryse-Phillips +9 more
TL;DR: The characteristic features of Bardet-Biedl syndrome are severe retinal dystrophy, dysmorphic extremities, obesity, renal abnormalities, and (in male patients only) hypogenitalism.
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