A novel microdeletion/microduplication syndrome of 19p13.13.
OBJECTIVE
Whole genome interrogation by array-based comparative genomic hybridization has led to a rapidly increasing number of discoveries of novel microdeletion and/or microduplication syndromes. We here describe the clinical and cytogenomic correlates of a novel microdeletion/microduplication of 19p13.13.


METHODS
Among patients referred to the Cytogenetics laboratory for array-based comparative genomic hybridization analysis, we identified four with a deletion and one with a duplication within 19p13.13. Confirmatory fluorescence in situ hybridization and parental studies were performed. Detailed clinical findings and array profiles were reviewed and compared.


RESULTS
Patients with deletions of 19p13.13 share a unique constellation of phenotypic abnormalities. In addition to developmental disabilities, the microdeletion manifested in overgrowth, macrocephaly, and ophthalmologic and gastrointestinal findings; in contrast, the single microduplication manifested in growth delay and microcephaly.


CONCLUSIONS
The consistent constellation of clinical findings associated with copy number variation of this region warrants the designation of microdeletion/microduplication syndrome of 19p13.13. An approximately 311-340 Kb smallest region of overlap encompassing 16 genes was identified. Candidate genes include MAST1, NFIX, and CALR. Identification of this syndrome has led to recommendations for diagnostic work-up and follow-up of patients with this copy number variant. Integration of detailed clinical and array data is critical for advancing both patient care and human genomic research.
Dolan
Michelle
M
Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA. dolan009@umn.edu
Mendelsohn
Nancy J
NJ
Pierpont
Mary Ella
ME
Schimmenti
Lisa A
LA
Berry
Susan A
SA
Hirsch
Betsy
B
D000015:Abnormalities, Multiple / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D017353:Gene Deletion; D020440:Gene Duplication; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008910:Minnesota; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome