Oral-facial-digital syndrome type VI: is C5orf42 really the major gene?

Oral-facial-digital type VI syndrome (OFDVI) is a rare phenotype of Joubert syndrome (JS). Recently, C5orf42 was suggested as the major OFDVI gene, being mutated in 9 of 11 families (82 %). We sequenced C5orf42 in 313 JS probands and identified mutations in 28 (8.9 %), most with a phenotype of pure JS. Only 2 out of 17 OFDVI patients (11.7 %) were mutated. A comparison of mutated vs. non-mutated OFDVI patients showed that preaxial and mesoaxial polydactyly, hypothalamic hamartoma and other congenital defects may predict C5orf42 mutations, while tongue hamartomas are more common in negative patients

Insights from Molecular Characterization of Adult Patients of Families with Multigenerational Diabetes Mellitus

Multigenerational diabetes of the adulthood is a mostly overlooked entity, simplistically comprised in the large basin of type 2 diabetes. The general aim we are pursuing in last years is to unravel the genetic causes of such form of diabetes. Identifying among families with multigenerational diabetes those carrying mutations in known monogenic diabetes genes is the first step to then concentrate on remaining pedigrees where to unravel new diabetogenes.Targeted Next Generation Sequencing of 27 monogenic diabetes-genes has been carried out in 55 family probands and identified mutations verified among their relatives by Sanger sequencing.Nine variants (in 8 probands) survived our filtering/prioritization strategy. After likelihood of causality assessment by established guidelines, 6 variants were classified as "pathogenetic/likely pathogenetic" and 2 as "of uncertain significance".Combining present with our previous data on the six genes causing the most common forms of maturity-onset diabetes of the young allows inferring that 23.6% families with multigenerational diabetes of the adulthood carry mutations in known monogenic diabetes-genes.Our findings indicate that the genetic background of hyperglycemia is unrecognized in the vast majority of families with multigenerational diabetes of the adulthood. These families now become the object of further research aimed at unraveling new diabetogenes

author response functional genome wide sirna screen identifies kiaa0586 as mutated in joubert syndrome

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