title: Expanding the genotype-phenotype correlation in subtelomeric 19p13.3 microdeletions using high resolution clinical chromosomal microarray analysis.
abstract: Structural rearrangements of chromosome 19p are rare, and their resulting phenotypic consequences are not well defined. This is the first study to report a cohort of eight patients with subtelomeric 19p13.3 microdeletions, identified using clinical chromosomal microarray analysis (CMA). The deletion sizes ranged from 0.1 to 0.86 Mb. Detailed analysis of the patients' clinical features has enabled us to define a constellation of clinical abnormalities that include growth delay, multiple congenital anomalies, global developmental delay, learning difficulties, and dysmorphic facial features. There are eight genes in the 19p13.3 region that may potentially contribute to the clinical phenotype via haploinsufficiency. Moreover, in silico genomic analysis of 19p13.3 microdeletion breakpoints revealed numerous highly repetitive sequences, suggesting LINEs/SINEs-mediated events in generating these microdeletions. Thus, subtelomeric 19p13.3 appears important for normal embryonic and childhood development. The clinical description of patients with deletions in this genomic interval will assist clinicians to identify and treat individuals with similar deletions.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas; Department of Pediatrics-Hematology-Oncology, Baylor College of Medicine and Texas Children's Cancer Center, Houston, Texas.
authors.forename: Sirisha
authors.initials: S
authors.lastname: Peddibhotla
authors.forename: Mohamed
authors.initials: M
authors.lastname: Khalifa
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Probst
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stein
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Harris
authors.forename: Debra L
authors.initials: DL
authors.lastname: Kearney
authors.forename: Gail H
authors.initials: GH
authors.lastname: Vance
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Bull
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Grange
authors.forename: Gunter H
authors.initials: GH
authors.lastname: Scharer
authors.forename: Sue-Hae L
authors.initials: SH
authors.lastname: Kang
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bacino
authors.forename: Sau W
authors.initials: SW
authors.lastname: Cheung
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
mesh_terms: D000328:Adult; D002648:Child; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D046228:Microarray Analysis; D016615:Telomere / Q000235:genetics*
keywords: 19p aberrations; 19p13.3 microdeletion; VACTERL; dysmorphic features; genomic microarray; global developmental delay; learning disability; multiple congenital anomalies; subtelomere