title: ANKRD11 variants cause variable clinical features associated with KBG syndrome and Coffin-Siris-like syndrome.
abstract: KBG syndrome (KBGS) is an autosomal dominant multiple congenital anomaly-intellectual disability syndrome, characterized by developmental delay with neurological involvements, macrodontia of the upper central incisors, characteristic facial dysmorphism and skeletal anomalies. Variants in ANKRD11 cause KBGS. We present five individuals from four families with ANKRD11 variants identified by whole-exome sequencing. Four of the five were clinically affected, and their diagnoses were varied. One was typical KBGS, two were Coffin-Siris syndrome-like (CSS), and one was intellectual disability with infantile spasms. One individual showed extremely mild phenotype. All individuals fulfilled the proposed diagnostic criteria for KBGS. Phenotypic features overlap between KBGS and CSS to some extent, and characteristic dental and fifth finger/toe findings can indicate differential diagnosis. These findings indicate that patients with ANKRD11 variants occupy a wide spectrum of intellectual disability, including clinically normal individuals. This is the first report highlighting the clinical overlap between KBGS and CSS and supporting the recently proposed clinical concept, in which transcriptional machineries are disrupted.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.|Clinical Genetics Department, Yokohama City University Hospital, Yokohama, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Miyatake
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Victorian Clinical Genetics Service, Murdoch Children's Research Institute, Melbourne, Australia.
authors.forename: Zornitza
authors.initials: Z
authors.lastname: Stark
authors.affiliation: Department of Pediatrics, Yodogawa Christian Hospital, Osaka City, Osaka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nabetani
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizuguchi
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtake
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.|Department of Biochemistry, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Hirotomo
authors.identifier: http://orcid.org/0000-0003-0723-0960
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D001848:Bone Diseases, Developmental / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005145:Face / Q000002:abnormalities*; D019066:Facies; D005260:Female; D014644:Genetic Variation; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008844:Micrognathism / Q000235:genetics*; D009333:Neck / Q000002:abnormalities*; D010641:Phenotype; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D014071:Tooth Abnormalities / Q000235:genetics*
chemical_list: C492515:ANKRD11 protein, human; D012097:Repressor Proteins