title: De novo mutations of the gene encoding the histone acetyltransferase KAT6B in two patients with Say-Barber/Biesecker/Young-Simpson syndrome.
abstract: The Say-Barber/Biesecker/Young-Simpson (SBBYS) type of the blepharophimosis-mental retardation syndrome group (Ohdo-like syndromes) is a multiple congenital malformation syndrome characterized by vertical narrowing and shortening of the palpebral fissures, ptosis, intellectual disability, hypothyroidism, hearing impairment, and dental anomalies. Mutations of the gene encoding the histone-acetyltransferase KAT6B have been recently identified in individuals affected by SBBYS syndrome. SBBYS syndrome-causing KAT6B mutations cluster in a ~1,700 basepair region in the 3' part of the large exon 18, while mutations located in the 5' region of the same exon have recently been identified to cause the genitopatellar syndrome (GPS), a clinically distinct although partially overlapping malformation-intellectual disability syndrome. Here, we present two children with clinical features of SBBYS syndrome and de novo truncating KAT6B mutations, including a boy who was diagnosed at the age of 4 months. Our results confirm the implication of KAT6B mutations in typical SBBYS syndrome and emphasize the importance of genotype-phenotype correlations at the KAT6B locus where mutations truncating the KAT6B protein at the amino-acid positions ~1,350-1,920 cause SBBYS syndrome.
authors: Institute of Pediatrics, Clinical Genetics Center, University of Debrecen, Medical & Health Science Center, Debrecen, Hungary. szakszon.katalin@gmail.com
authors: Katalin
authors: K
authors: Szakszon
authors: Carmelo
authors: C
authors: Salpietro
authors: Naseebullah
authors: N
authors: Kakar
authors: Alida C
authors: AC
authors: Knegt
authors: Éva
authors: É
authors: Oláh
authors: Bruno
authors: B
authors: Dallapiccola
authors: Guntram
authors: G
authors: Borck
mesh_terms: D000015:Abnormalities, Multiple; D001483:Base Sequence; D016569:Blepharophimosis / Q000175:diagnosis / Q000235:genetics*; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D003409:Congenital Hypothyroidism / Q000175:diagnosis / Q000235:genetics*; D005091:Exons; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D051548:Histone Acetyltransferases / Q000235:genetics*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D007593:Joint Instability / Q000175:diagnosis / Q000235:genetics*; D059785:Karyotype; D008297:Male; D009154:Mutation; D010641:Phenotype
chemical_list: D051548:Histone Acetyltransferases; C487137:KAT6B protein, human