Researchers report that two clinically different inherited syndromes are in fact variations of the same disorder. The scientists studied Bardet-Biedl syndrome (BBS), a rare so-called ciliopathy that is characterized by a combination of ailments and caused by faulty cilia. Recently they began looking at another disease, Meckel-Gruber syndrome (MKS), which also shows cilia dysfunction but is clinically distinct from BBS. MKS is also generally associated with prenatal or newborn death.
The researchers sequenced the MKS genes from 200 BBS patients and found six families that in addition to carrying BBS genetic mutations also carried mutations in MKS genes.
The investigators further examined these genes by silencing them in zebrafish. They found that knocking out the MKS genes in the zebrafish mimicked BBS-knockout fish. Then mutant versions of MKS genes in BBS fish were tested. The team reports that three genes originally attributed to MKS—MKS1, MKS3, and CEP290—do indeed cause BBS or render the BBS defects more pronounced, increasing the number of BBS-associated genes to 14 in total.
“From a clinical perspective, these two syndromes look nothing alike, but molecularly, the genes involved clearly participate in the same fundamental processes,” comments Nicholas Katsanis, Ph.D., an associate professor of ophthalmology at the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins. “This means that Meckel-Gruber and Bardet-Biedel actually represent a continuum of one disease.”
The research was conducted by investigators at Johns Hopkins, Université Louis Pasteur, University College London, King Fahad Hospital, Baylor College of Medicine, Hadassah–Hebrew University Hospital, and Institut Pasteur de Montevideo. The study was reported online on March 9 and will appear in the April issue of Nature Genetics.