title: Truncating mutations in APP cause a distinct neurological phenotype.
abstract: Dominant missense mutations in the amyloid β (Aβ) precursor protein (APP) gene have been implicated in early onset Alzheimer disease. These mutations alter protein structure to favor the pathologic production of Aβ. We report that homozygous nonsense mutations in APP are associated with decreased somatic growth, microcephaly, hypotonia, developmental delay, thinning of the corpus callosum, and seizures. We compare the phenotype of this case to those reported in mouse models and demonstrate multiple similarities, strengthening the role of amyloid precursor protein in normal brain function and development. Ann Neurol 2016;80:456-460.
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
authors.forename: Steven
authors.initials: S
authors.lastname: Klein
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
authors.forename: Alexander
authors.initials: A
authors.lastname: Goldman
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
authors.forename: Hane
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Radiology.
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Ghahremani
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
authors.forename: Viraj
authors.initials: V
authors.lastname: Bhakta
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.|Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.|Division of Medical Genetics, Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Nelson
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. julianmartinez@mednet.ucla.edu.|Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. julianmartinez@mednet.ucla.edu.|Jonsson Cancer Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. julianmartinez@mednet.ucla.edu.
authors.forename: Julian A
authors.identifier: http://orcid.org/0000-0001-6776-6949
authors.initials: JA
authors.lastname: Martinez-Agosto
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D003241:Consanguinity; D003337:Corpus Callosum / Q000473:pathology*; D002658:Developmental Disabilities / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D009123:Muscle Hypotonia / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D012640:Seizures / Q000235:genetics*
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor