A Novel Familial BBS12 Mutation Associated with a Mild Phenotype: Implications for Clinical and Molecular Diagnostic Strategies.

Molecular Syndromology
B PawlikB Wollnik

Abstract

Bardet-Biedl syndrome (BBS) is an autosomal recessively inherited ciliopathy mainly characterized by rod-cone dystrophy, postaxial polydactyly, obesity, renal tract anomalies, and hypogonadism. To date, 14 BBS genes, BBS1 to BBS14, have been identified, accounting for over 75% of mutations in BBS families. In this study, we present a consanguineous family from Pakistan with postaxial polydactyly and late-onset retinal dysfunction. Adult affected individuals did not show any renal or genital anomalies, obesity, mental retardation or learning difficulties and did thus not fulfill the proposed clinical diagnostic criteria for BBS. We mapped the disease in this family to the BBS12 locus on chromosome 4q27 and identified the novel homozygous p.S701X nonsense mutation in BBS12 in all three affected individuals of this family. We conclude that BBS12 mutations might cause a very mild phenotype, which is clinically not diagnosed by the current diagnostic criteria for BBS. Consequently, we suggest the use of less strict diagnostic criteria in familial BBS families with mild phenotypic expression.

References

Oct 12, 1989·The New England Journal of Medicine·J S GreenW Pryse-Phillips
Sep 8, 1988·The New England Journal of Medicine·J D HarnettP S Parfrey
Nov 6, 1995·American Journal of Medical Genetics·R CarmiV C Sheffield
Feb 1, 1997·Journal of Medical Genetics·P L BealesF A Flinter
Oct 24, 2001·Human Molecular Genetics·N KatsanisP L Beales
Oct 3, 2002·Nature Reviews. Genetics·Jose L Badano, Nicholas Katsanis
Feb 5, 2003·American Journal of Human Genetics·José L BadanoNicholas Katsanis
Dec 6, 2005·Nature·Jose L BadanoNicholas Katsanis
Apr 4, 2006·Nature Genetics·Corinne StoetzelHélène Dollfus
Apr 12, 2006·Proceedings of the National Academy of Sciences of the United States of America·Annie P ChiangVal C Sheffield
May 26, 2006·Annual Review of Genomics and Human Genetics·Jose L BadanoNicholas Katsanis
Aug 8, 2006·Current Biology : CB·Wallace F Marshall, Shigenori Nonaka
Mar 16, 2007·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Jonathan L Tobin, Philip L Beales
Apr 28, 2007·Science·UNKNOWN Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical RShaun Purcell
Mar 3, 2009·The Journal of Clinical Investigation·Norann A Zaghloul, Nicholas Katsanis

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Citations

Feb 23, 2012·European Journal of Human Genetics : EJHG·Leen Abu-SafiehFowzan S Alkuraya
Apr 8, 2014·Genes·Muhammad Imran KhanRaheel Qamar
Apr 12, 2011·Progress in Retinal and Eye Research·A MockelH Dollfus
Jun 18, 2015·Journal of Medical Genetics·Sheila Castro-SánchezDiana Valverde
Apr 6, 2011·Ophthalmic Genetics·Gail BillingsleyElise Héon
May 12, 2015·Case Reports in Nephrology·Cem SahinMustafa Levent
Jan 15, 2016·Clinical Genetics·S A KhanS Khan
Aug 11, 2011·Korean journal of pediatrics·Se-Hyung SonJung-Hwan Choi
Oct 20, 2018·Biomédica : revista del Instituto Nacional de Salud·Luz Yaqueline LadinoOrietta Ivonne Beltrán
Mar 16, 2017·Cold Spring Harbor Perspectives in Biology·Kinga M BujakowskaEric A Pierce
Dec 22, 2017·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·M PigeyreD Meyre

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