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Whole exome sequencing identifies aPOLRIDmutation segregating in a father and two daughters with findings of Klippel-Feil and Treacher Collins syndromes
- Source :
- American Journal of Medical Genetics Part A. 167:95-102
- Publication Year :
- 2014
- Publisher :
- Wiley, 2014.
-
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. © 2014 Wiley Periodicals, Inc.
- Subjects :
- Male
DNA Mutational Analysis
Nuclear Family
Fathers
Chromosome Segregation
Genetics
Humans
Medicine
Missense mutation
Exome
Family
Craniofacial
Child
Genetic Association Studies
Genetics (clinical)
Exome sequencing
business.industry
Genetic heterogeneity
fungi
Infant, Newborn
Computational Biology
DNA-Directed RNA Polymerases
medicine.disease
Hypoplasia
Pedigree
Klippel feil
Klippel-Feil Syndrome
Mutation
Mutation (genetic algorithm)
Female
business
Treacher Collins syndrome
Mandibulofacial Dysostosis
Subjects
Details
- ISSN :
- 15524825
- Volume :
- 167
- Database :
- OpenAIRE
- Journal :
- American Journal of Medical Genetics Part A
- Accession number :
- edsair.doi.dedup.....48cffd202acd29e60f9f4e56cee2fe42