title: Increased bone turnover, osteoporosis, progressive tibial bowing, fractures, and scoliosis in a patient with a final-exon SATB2 frameshift mutation.
abstract: Haploinsufficiency of SATB2 causes cleft palate, intellectual disability with deficient speech, facial and dental abnormalities, and other variable features known collectively as SATB2-associated syndrome. This phenotype was accompanied by osteoporosis, fractures, and tibial bowing in two previously reported adult patients; each possessed SATB2 mutations either predicted or demonstrated to escape nonsense-mediated decay, suggesting that the additional bone defects result from a dominant negative effect and/or age-dependent penetrance. These hypotheses remain to be confirmed, as do the specific downstream defects causing bone abnormalities. We report a SATB2 mutation (c.2018dupA; p.(H673fs)) in a 15-year-old patient whose SATB2-associated syndrome phenotype is accompanied by osteoporosis, fractures, progressive tibial bowing, and scoliosis. As this homeodomain-disrupting and predicted truncating mutation resides within the final exon of SATB2, escape from nonsense-mediated decay is likely. Thus, we provide further evidence of bone phenotypes beyond those typically associated with SATB2-associated syndrome in individuals with potential dominant-negative SATB2 alleles, as well as evidence for age-dependence of bone features. Elevations in alkaline phosphatase, urinary N-telopeptide/creatinine ratio, and osteocalcin in the patient indicate increased bone turnover. We propose surveillance and treatment with osteoclast inhibitors to prevent fractures and to slow progressive bone deformities. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Boone
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yiu Man
authors.initials: YM
authors.lastname: Chan
authors.affiliation: Texas Children's Hospital, Houston, Texas.
authors.forename: Jill V
authors.initials: JV
authors.lastname: Hunter
authors.affiliation: Texas Children's Hospital, Houston, Texas.
authors.forename: Louis E
authors.initials: LE
authors.lastname: Pottkotter
authors.affiliation: Department of Orthopedic Surgery, UT Health Science Center at Houston, Houston, Texas.
authors.forename: Nelson A
authors.initials: NA
authors.lastname: Davino
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine.|Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine.|Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas.
authors.forename: Joke
authors.initials: J
authors.lastname: Beuten
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine. cbacino@bcm.edu.|Texas Children's Hospital, Houston, Texas. cbacino@bcm.edu.|Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas. cbacino@bcm.edu.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bacino
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D000293:Adolescent; D015415:Biomarkers; D016723:Bone Remodeling / Q000235:genetics; D001921:Brain / Q000473:pathology; D005091:Exons; D050723:Fractures, Bone / Q000235:genetics; D016368:Frameshift Mutation; D057895:Haploinsufficiency; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics*; D010024:Osteoporosis / Q000235:genetics; D010641:Phenotype; D011859:Radiography; D012600:Scoliosis / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D015415:Biomarkers; D036961:Matrix Attachment Region Binding Proteins; C521297:SATB2 protein, human; D014157:Transcription Factors
keywords: Glass syndrome; SATB2; bone remodeling; osteoclastic activity; tibial bowing