Novel truncating variants expand the phenotypic spectrum of KAT6B‐related disorders

• Published in: American journal of medical genetics. Part A Vol. 179; no. 2; pp. 290 - 294
• Main Authors: Brea‐Fernández, Alejandro, Dacruz, David, Eirís, Jesús, Barros, Francisco, Carracedo, Ángel
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.02.2019; Wiley Subscription Services, Inc
• Subjects: Abnormalities, Multiple - genetics; Abnormalities, Multiple - physiopathology; Blepharophimosis - genetics; Blepharophimosis - physiopathology; Child; Congenital Hypothyroidism - genetics; Congenital Hypothyroidism - physiopathology; Craniofacial Abnormalities - genetics; Craniofacial Abnormalities - physiopathology; Exons - genetics; Facies; Genitopatellar syndrome; Heart Defects, Congenital - genetics; Heart Defects, Congenital - physiopathology; Heterozygote; Histone Acetyltransferases - genetics; Humans; intellectual disability; Intellectual Disability - genetics; Intellectual Disability - physiopathology; Joint Instability - genetics; Joint Instability - physiopathology; KAT6B; KAT6B‐related disorders; Kidney - abnormalities; Kidney - physiopathology; Male; Mutation; Patella - abnormalities; Patella - physiopathology; Phenotype; Phenotypes; Psychomotor Disorders - genetics; Psychomotor Disorders - physiopathology; Say‐Barber‐Biesecker‐Young‐Simpson syndrome; Scrotum - abnormalities; Scrotum - physiopathology; Urogenital Abnormalities - genetics; Urogenital Abnormalities - physiopathology; Say-Barber-Biesecker-Young-Simpson syndrome; KAT6B-related disorders; Genitopatellar syndrome; KAT6B; intellectual disability
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.60689

Say–Barber–Biesecker–Young–Simpson syndrome (SBBYSS) and Genitopatellar syndrome (GTPTS) are very rare conditions caused by KAT6B truncating variants. Because of both syndromes often share common features the associated phenotypes are usually grouped under the term “KAT6B‐related disorders.” However, particular signs of each syndrome have been reported and their appearance seems to be dependent on where the KAT6B variant is located. Thus, whereas truncating variants associated with SBBYSS have their highest density in the distal part of exon 18, those resulting in GTPTS are distributed between the end of exon 17 and beginning of exon 18. Here, we reported two de novo heterozygous KAT6B truncating variants. The first variant (c.5802delA; p.A1935Pfs*16), identified in a boy with SSBYSS phenotype, resulting in the most distal KAT6B truncating variant reported up‐to‐date in the scientific literature. The second variant (c.3152delG; p.S1051Tfs*63), located in a region hitherto defined as specific of SBBYSS, seems to cause an overlapping SBBYSS/GTPTS phenotype. The clinical and genetic characterization of these patients could contribute to the understanding of the KAT6B‐related disorders.