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http://purl.uniprot.org/citations/26900326http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26900326http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26900326http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

To identify the causative mutation in two siblings from a consanguineous family in India with retinitis pigmentosa (RP) and polydactyly without other findings of Bardet-Biedl syndrome (BBS). We also performed functional characterization of the mutant protein to explore its role in this limited form of BBS.

Methods

The siblings underwent a thorough ophthalmological examination, including retinal optical coherence tomography (OCT) imaging, and an extensive physical examination with abdominal ultrasonography to characterize the disease phenotype. Next-generation sequencing (NGS) using a panel targeting retinal degeneration genes was performed on genomic DNA samples from the siblings and parents. Upon identification of the causative mutation, functional characterization was accomplished by performing protein-protein interaction studies in human embryonic kidney (HEK-293T) and human adult retinal pigmented epithelium (ARPE-19) cells.

Results

The two siblings showed signs of RP and polydactyly. The patients did not have truncal obesity, renal anomalies, hydrometrocolpos, congenital heart disease, or overt cognitive defects. NGS identified a homozygous c.1184A>G mutation in the MKKS/BBS6 gene in both patients resulting in a p.H395R substitution in the MKKS/BBS6 protein. This mutant protein decreased the interaction of MKKS/BBS6 with BBS12 but did so to a different extent in the HEK-293T versus ARPE-19 cells. Nonetheless, the effect of the H395R variant on disrupting interactions with BBS12 was not as profound as other reported MKKS/BBS6 mutations associated with syndromic RP.

Conclusions

We identified a novel H395R substitution in MKKS/BBS6 that results in a unique phenotype of only RP and polydactyly. Our observations reaffirm the notion that mutations in MKKS/BBS6 cause phenotypic heterogeneity and do not always result in classic MKKS or BBS findings."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Gupta R."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Gupta R."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Nguyen A."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Nguyen A."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Angara R."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Angara R."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Hulleman J.D."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Hulleman J.D."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Mahindrakar A."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Mahindrakar A."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Mootha V.V."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Mootha V.V."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Murugan S."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Murugan S."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Ramprasad V.L."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Ramprasad V.L."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Sankurathri C."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/author"Sankurathri C."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/name"Mol. Vis."xsd:string
http://purl.uniprot.org/citations/26900326http://purl.uniprot.org/core/name"Mol. Vis."xsd:string
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