Analysis of MLL2 gene in the first Brazilian family with Kabuki syndrome.

Most patients with Kabuki syndrome (KS) are the only person in their family with the condition. However, familial cases of KS have been described showing evidence that this syndrome can be inherited as a dominant trait with variable expressivity. We report on two related individuals with facial findings characteristic of KS. The proposita had arched eyebrows, long and upward slanting palpebral fissures, cleft lip and palate, retromicrognathia, brachydactyly of hands and feet, stubby fingers, nail hypoplasia, and prominent finger pads. Her mother had eyebrows with dispersed lateral half, long and upward slanting palpebral fissures, retrognathia, abnormal and posteriorly rotated ears, prominent finger pads, brachydactyly of feet, learning difficulties, and psychomotor development delay. DNA sequencing revealed a novel missense mutation in the MLL2 gene in both the proposita and her mother. The mutation (p.R5432Q) was found in the exon 51, within the SET domain of the gene, which confers methyltransferase activity on the protein. Therefore, the epigenetic and transcriptional regulatory properties of this protein may be altered and this suggests that the mutation is the cause of phenotype observed in both the patient and her mother. The clinical signs and the molecular evidence in this family further support the notion that KS is an autosomal dominant condition with variable expressivity. To our knowledge this is the first report of a Brazilian family with recurrence of this syndrome.

Further characterization of microdeletion syndrome involving 2p15-p16.1.

We report on a patient presenting with cognitive delay, prenatal and postnatal growth deficiency, microcephaly, ptosis of eyelids, high and broad nasal root, and camptodactyly. Analysis of a dense whole genome single-nucleotide polymorphism (SNP) array showed a de novo 3.35 Mb deletion on 2p15-p16.1. In order to study the parental origin of the deletion we analyzed selected SNPs in the deleted area in the proband and her parents showing Mendelian incompatibilities suggesting a de novo deletion on the chromosome of paternal origin. Based on the five cases described previously in the literature, we have narrowed the critical region responsible for the 2p15-p16.1 microdeletion syndrome phenotype. The critical region does not include the VRK2 gene that had been speculated to have a role in cortical dysplasia. However, the association of the VRK2 gene with cortical dysplasia remains to be determined, as MRI imaging of the brain and gene content of the 2p15-16 deletion becomes established in more patients.