title: Disruption of a synaptotagmin (SYT14) associated with neurodevelopmental abnormalities.
abstract: We report cytogenetic and molecular studies of a de novo, apparently balanced t(1;3)(q32.1;q25.1) identified in a 12-year-old female (designated DGAP128) with cerebral atrophy, macrocephaly seizures, and developmental delay. A combination of fluorescence in situ hybridization (FISH) and Southern blot analysis demonstrated disruption of a synaptotagmin gene (SYT14) at the 1q32 breakpoint. Expression of SYT14 in human brain was confirmed using Northern analysis. Because members of the synaptotagmin family of proteins function as sensors that link changes in calcium levels with a variety of biological processes, including neurotransmission and hormone-responsiveness, SYT14 is an intriguing candidate gene for the abnormal development in this child. This is the first known constitutional rearrangement of SYT14, and further systematic genetic analysis and clinical studies of DGAP128 may offer unique insights into the role of SYT14 in neurodevelopment.
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Quintero-Rivera
authors.forename: Alicia
authors.initials: A
authors.lastname: Chan
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Donovan
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Azra H
authors.initials: AH
authors.lastname: Ligon
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D001284:Atrophy; D015152:Blotting, Northern; D015139:Blotting, Southern; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002871:Chromosome Banding; D019457:Chromosome Breakage; D002878:Chromosomes, Human, Pair 1; D002893:Chromosomes, Human, Pair 3; D002658:Developmental Disabilities / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D012640:Seizures / Q000473:pathology; D050857:Synaptotagmins / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D050857:Synaptotagmins