De novo mutations of the gene encoding the histone acetyltransferase KAT6B in two patients with Say‐Barber/Biesecker/Young‐Simpson syndrome

• Published in: American journal of medical genetics. Part A 2013-04, Vol.161 (4), p.884-888
• Main Authors: Szakszon, Katalin, Salpietro, Carmelo, Kakar, Naseebullah, Knegt, Alida C., Oláh, Éva, Dallapiccola, Bruno, Borck, Guntram
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple; Age; Base Sequence; blepharophimosis; Blepharophimosis - diagnosis; Blepharophimosis - genetics; Child, Preschool; Comparative Genomic Hybridization; Congenital Hypothyroidism - diagnosis; Congenital Hypothyroidism - genetics; Exons; Facies; Female; Genetic Association Studies; Heart Defects, Congenital - diagnosis; Heart Defects, Congenital - genetics; Heterozygote; Histone Acetyltransferases - genetics; Humans; Infant; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Joint Instability - diagnosis; Joint Instability - genetics; Karyotype; KAT6B; Male; mental retardation; Mutation; patellar hypoplasia; Phenotype; Say‐Barber/Biesecker/Young‐Simpson syndrome
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.35848

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. © 2013 Wiley Periodicals, Inc.