title: Compound heterozygosity for mutations in PAX6 in a patient with complex brain anomaly, neonatal diabetes mellitus, and microophthalmia.
abstract: We report on a patient with trisomy 21, microophthalmia, neonatal diabetes mellitus, hypopituitarism, and a complex structural brain anomaly who was a member of a large bilineal family with eye anomalies. The patient inherited a different mutation in PAX6 from each parent and is the only known living and second reported patient with compound heterozygosity for mutations in PAX6. PAX6 is a transcription factor involved in eye and brain development and has roles in pancreatic and pituitary development. Clinical evaluation of the propositus and his parents demonstrated the effects of mutations of differing severity in multiple individuals.
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Solomon
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Pineda-Alvarez
authors.forename: Joan Z
authors.initials: JZ
authors.lastname: Balog
authors.forename: Donald
authors.initials: D
authors.lastname: Hadley
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Gropman
authors.forename: Radha
authors.initials: R
authors.lastname: Nandagopal
authors.forename: Joan C
authors.initials: JC
authors.lastname: Han
authors.forename: Jin S
authors.initials: JS
authors.lastname: Hahn
authors.forename: Delphine
authors.initials: D
authors.lastname: Blain
authors.forename: Brian
authors.initials: B
authors.lastname: Brooks
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
mesh_terms: D001921:Brain / Q000002:abnormalities*; D002675:Child, Preschool; D048909:Diabetes Complications / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008850:Microphthalmos / Q000150:complications* / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins