title: A patient with a unique frameshift mutation in GPC3, causing Simpson-Golabi-Behmel syndrome, presenting with craniosynostosis, penoscrotal hypospadias, and a large prostatic utricle.
abstract: We present a Hispanic male with the clinical and molecular diagnosis of Simpson-Golabi-Behmel syndrome (SGBS). The patient was born with multiple anomalies not entirely typical of SGBS patients, including penoscrotal hypospadias, a large prostatic utricle, and left coronal craniosynostosis. In addition, he demonstrated endocrine anomalies including a low random cortisol level suspicious for adrenal insufficiency and low testosterone level. To our knowledge, this is the first report of a prostatic utricle in SGBS and the second report of craniosynostosis. The unique disease-causing mutation likely arose de novo in the mother. It is a deletion-insertion that leads to a frameshift at the p.p. S359 [corrected] residue of GPC3 and a premature stop codon after five more amino acids. p. S359 [corrected] is the same residue that is normally cleaved by the Furin convertase, although the significance of this novel mutation with respect to the patient's multiple anomalies is unknown. We present this case as the perinatal course of a patient with unique features of SGBS and a confirmed molecular diagnosis.
authors.affiliation: Department of Cellular and Structural Biology, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Diana D
authors.initials: DD
authors.lastname: Villarreal
authors.forename: Humberto
authors.initials: H
authors.lastname: Villarreal
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Paez
authors.forename: Dennis
authors.initials: D
authors.lastname: Peppas
authors.forename: Jane
authors.initials: J
authors.lastname: Lynch
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Roeder
authors.forename: George C
authors.initials: GC
authors.lastname: Powers
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000503:physiopathology; D000328:Adult; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D003398:Craniosynostoses / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D012734:Disorders of Sex Development / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D005260:Female; D016368:Frameshift Mutation; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005877:Gigantism / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D053673:Glypicans / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D057089:Pathology, Molecular; D010413:Penis / Q000002:abnormalities / Q000503:physiopathology; D011467:Prostate / Q000503:physiopathology*; D012444:Saccule and Utricle / Q000503:physiopathology*; D012611:Scrotum / Q000002:abnormalities / Q000503:physiopathology; D014522:Urethral Diseases / Q000150:complications / Q000235:genetics / Q000503:physiopathology
chemical_list: C105937:GPC3 protein, human; D053673:Glypicans
keywords: Simpson-Golabi-Behmel syndrome; adrenal insufficiency; ambiguous genitalia; coronal synostosis; craniosynostosis; diaphragmatic hernia; glypican 3; hypospadias; large for gestational age; prostatic utricle