A patient showing features of both SBBYSS and GPS supports the concept of a KAT6B-related disease spectrum, with mutations in mid-exon 18 possibly leading to combined phenotypes.

Abstract

Genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) are two distinct clinically overlapping syndromes caused by de novo heterozygous truncating mutations in the KAT6B gene encoding lysine acetyltransferase 6B, a part of the histone H3 acetyltransferase complex. We describe an 8-year-old girl with a KAT6B mutation and a combined GPS/SBBYSS phenotype. The comparison of this patient with 61 previously published cases with KAT6B mutations and GPS, SBBYSS or combined GPS/SBBYSS phenotypes allowed us to separate the KAT6B mutations into four groups according to their position in the gene (reflecting nonsense mediated RNA decay and protein domains) and their clinical outcome. We suggest that mutations in mid-exon 18 corresponding to the C-terminal end of the acidic (Asp/Glu-rich) domain of KAT6B may have more variable expressivity leading to GPS, SBBYSS or combined phenotypes, in contrast to defects in other regions of the gene which contribute more specifically to either GPS or SBBYSS. Notwithstanding the clinical overlap, our cluster analysis of phenotypes of all known patients with KAT6B mutations supports the existence of two clinical entities, GPS and SBBYSS, as poles within the KAT6B-related disease spectrum. The awareness of these phenomena is important for qualified genetic counselling of patients with KAT6B mutations.

• Authors: Marketa Vlckova, Martina Simandlova, Pavel Zimmermann, Viktor Stranecky, Hana Hartmannova, Katerina Hodanova, Marketa Havlovicova, Miroslava Hancarova, Stanislav Kmoch, Zdenek Sedlacek
• Journal: European journal of medical genetics (Eur J Med Genet) Vol. 58 Issue 10 Pg. 550-5 (Oct 2015) ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 26370006 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Chemical References

• Histone Acetyltransferases
• KAT6B protein, human

Topics

• Base Sequence
• Blepharophimosis (diagnosis, genetics)
• Child
• Congenital Hypothyroidism (diagnosis, genetics)
• Craniofacial Abnormalities (diagnosis, genetics)
• Exons
• Facies
• Female
• Heart Defects, Congenital (diagnosis, genetics)
• Histone Acetyltransferases (genetics)
• Humans
• Intellectual Disability (diagnosis, genetics)
• Joint Instability (diagnosis, genetics)
• Kidney (abnormalities)
• Molecular Sequence Data
• Mutation
• Patella (abnormalities)
• Phenotype
• Psychomotor Disorders (diagnosis, genetics)
• Scrotum (abnormalities)
• Urogenital Abnormalities (diagnosis, genetics)