title: Analysis of MLL2 gene in the first Brazilian family with Kabuki syndrome.
abstract: 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.
authors: Department of Clinical Genetics, Hospital of Rehabilitation of Craniofacial Anomalies, University of São Paulo (HRCA-USP), Bauru, São Paulo, Brazil. nancykn@centrinho.usp.br
authors: Nancy Mizue
authors: NM
authors: Kokitsu-Nakata
authors: Aline Lourenço
authors: AL
authors: Petrin
authors: Jason Paul
authors: JP
authors: Heard
authors: Siulan
authors: S
authors: Vendramini-Pittoli
authors: Laura E
authors: LE
authors: Henkle
authors: Daniela Vera Cruz
authors: DV
authors: dos Santos
authors: Jeffrey Clark
authors: JC
authors: Murray
authors: Antonio
authors: A
authors: Richieri-Costa
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D001938:Brazil; D004268:DNA-Binding Proteins / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D005260:Female; D006402:Hematologic Diseases / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D015837:Vestibular Diseases / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins