Search

Your search keyword '"Sisco, Kathleen"' showing total 2 results
Start Over Author "Sisco, Kathleen" Topic dna-binding proteins
2 results on '"Sisco, Kathleen"'

1. Discovery of a novel CHD7 CHARGE syndrome variant by integrated omics analyses.

Author

Granadillo JL, Wegner DJ, Paul AJ, Willing M, Sisco K, Tedder ML, Sadikovic B, Wambach JA, Baldridge D, and Cole FS

Subjects
CHARGE Syndrome complications, CHARGE Syndrome pathology, Child, Child, Preschool, Choanal Atresia complications, Choanal Atresia pathology, Coloboma complications, Coloboma pathology, Heart Defects, Congenital complications, Heart Defects, Congenital pathology, Humans, Infant, Introns genetics, Male, Mutation genetics, Phenotype, Exome Sequencing, CHARGE Syndrome genetics, Choanal Atresia genetics, Coloboma genetics, DNA Helicases genetics, DNA-Binding Proteins genetics, Heart Defects, Congenital genetics
Abstract

Chromodomain helicase DNA-binding protein 7 (CHD7) pathogenic variants are identified in more than 90% of infants and children with CHARGE (Coloboma of the iris, retina, and/or optic disk; congenital Heart defects, choanal Atresia, Retardation of growth and development, Genital hypoplasia, and characteristic outer and inner Ear anomalies and deafness) syndrome. Approximately, 10% of cases have no known genetic cause identified. We report a male child with clinical features of CHARGE syndrome and nondiagnostic genetic testing that included chromosomal microarray, CHD7 sequencing and deletion/duplication analysis, SEMA3E sequencing, and trio exome and whole-genome sequencing (WGS). We used a comprehensive clinical assessment, genome-wide methylation analysis (GMA), reanalysis of WGS data, and CHD7 RNA studies to discover a novel variant that causes CHD7 haploinsufficiency. The 7-year-old Hispanic male proband has typical phenotypic features of CHARGE syndrome. GMA revealed a CHD7-associated epigenetic signature. Reanalysis of the WGS data with focused bioinformatic analysis of CHD7 detected a novel, de novo 15 base pair deletion in Intron 4 of CHD7 (c.2239-20_2239-6delGTCTTGGGTTTTTGT [NM_017780.3]). Using proband RNA, we confirmed that this novel deletion causes CHD7 haploinsufficiency by disrupting the canonical 3' splice site and introducing a premature stop codon. Integrated genomic, epigenomic, and transcriptome analyses discovered a novel CHD7 variant that causes CHARGE syndrome., (© 2020 Wiley Periodicals LLC.)

Published
2021
Full Text
View/download PDF

2. Phenotypic expansion of KMT2D-related disorder: Beyond Kabuki syndrome.

Author

Baldridge D, Spillmann RC, Wegner DJ, Wambach JA, White FV, Sisco K, Toler TL, Dickson PI, Cole FS, Shashi V, and Grange DK

Subjects
Abnormalities, Multiple diagnostic imaging, Abnormalities, Multiple pathology, Adolescent, Adult, Breast diagnostic imaging, Breast physiopathology, Breast Diseases, Child, Congenital Abnormalities diagnostic imaging, Congenital Abnormalities physiopathology, Face diagnostic imaging, Face pathology, Female, Hematologic Diseases diagnostic imaging, Hematologic Diseases pathology, Humans, Loss of Function Mutation genetics, Male, Mutation genetics, Phenotype, Vestibular Diseases diagnostic imaging, Vestibular Diseases pathology, Exome Sequencing, Young Adult, Abnormalities, Multiple genetics, Breast abnormalities, Congenital Abnormalities genetics, DNA-Binding Proteins genetics, Face abnormalities, Genetic Predisposition to Disease, Hematologic Diseases genetics, Neoplasm Proteins genetics, Vestibular Diseases genetics
Abstract

Pathogenic variants in KMT2D, which encodes lysine specific methyltransferase 2D, cause autosomal dominant Kabuki syndrome, associated with distinctive dysmorphic features including arched eyebrows, long palpebral fissures with eversion of the lower lid, large protuberant ears, and fetal finger pads. Most disease-causing variants identified to date are putative loss-of-function alleles, although 15-20% of cases are attributed to missense variants. We describe here four patients (including one previously published patient) with de novo KMT2D missense variants and with shared but unusual clinical findings not typically seen in Kabuki syndrome, including athelia (absent nipples), choanal atresia, hypoparathyroidism, delayed or absent pubertal development, and extreme short stature. These individuals also lack the typical dysmorphic facial features found in Kabuki syndrome. Two of the four patients had severe interstitial lung disease. All of these variants cluster within a 40-amino-acid region of the protein that is located just N-terminal of an annotated coiled coil domain. These findings significantly expand the phenotypic spectrum of features associated with variants in KMT2D beyond those seen in Kabuki syndrome and suggest a possible new underlying disease mechanism for these patients., (© 2020 Wiley Periodicals, Inc.)

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results