Homozygous mutation in CEP19, a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly

Bardet-Biedl syndrome (BBS) presents a complex phenotype. We discovered that CEP19 gene is defective in a Pakistani family with many members having postaxial polydactyly plus variable other clinical features including rod-cone dystrophy, obesity, intellectual disability, renal malformation, developmental delay, dental anomalies, speech disorder and enlarged fatty liver. We also found different combinations of modifier alleles that exacerbate disease severity in patients. Those alleles are highly significantly more abundant in our patients than in a control group. Another mutation in CEP19 has been reported to cause morbid obesity; however, our patients are not all even obese. Our findings add to the complex genetics of the disease. (By Professor Aslıhan Tolun, http://jmg.bmj.com/content/early/2017/11/09/jmedgenet-2017-104758)