Faculty Collaboration Database

Whole exome sequencing identifies a POLRID mutation segregating in a father and two daughters with findings of Klippel-Feil and Treacher Collins syndromes. Am J Med Genet A 2015 Jan;167A(1):95-102

Date

10/29/2014

Pubmed ID

25348728

DOI

10.1002/ajmg.a.36799

Scopus ID

2-s2.0-84919632833 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

We report on a father and his two daughters diagnosed with Klippel-Feil syndrome (KFS) but with craniofacial differences (zygomatic and mandibular hypoplasia and cleft palate) and external ear abnormalities suggestive of Treacher Collins syndrome (TCS). The diagnosis of KFS was favored, given that the neck anomalies were the predominant manifestations, and that the diagnosis predated later recognition of the association between spinal segmentation abnormalities and TCS. Genetic heterogeneity and the rarity of large families with KFS have limited the ability to identify mutations by traditional methods. Whole exome sequencing identified a nonsynonymous mutation in POLR1D (subunit of RNA polymerase I and II): exon2:c.T332C:p.L111P. Mutations in POLR1D are present in about 5% of individuals diagnosed with TCS. We propose that this mutation is causal in this family, suggesting a pathogenetic link between KFS and TCS.

Author List

Giampietro PF, Armstrong L, Stoddard A, Blank RD, Livingston J, Raggio CL, Rasmussen K, Pickart M, Lorier R, Turner A, Sund S, Sobrera N, Neptune E, Sweetser D, Santiago-Cornier A, Broeckel U

Authors

Robert D. Blank PhD, MD Emeritus Professor in the Medicine department at Medical College of Wisconsin
Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin
Amy Turner Research Scientist I in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Child
Chromosome Segregation
Computational Biology
DNA Mutational Analysis
DNA-Directed RNA Polymerases
Exome
Family
Fathers
Female
Genetic Association Studies
Humans
Infant, Newborn
Klippel-Feil Syndrome
Male
Mandibulofacial Dysostosis
Mutation
Nuclear Family
Pedigree