Abstract | BACKGROUND: CASE PRESENTATION: A 3-month-old boy was referred for head titubation and tremulous movements of the trunk. Multiple petechiae also developed on his face and trunk at the age of 5 months. Extensive evaluation, including brain magnetic resonance imaging, hematologic tests, and bone-marrow evaluation, revealed cerebellar atrophy and aplastic anemia. His elder brother exhibited a similar clinical presentation and died from sepsis after hematopoietic stem cell transplantation. Although skin pigmentation or nail dystrophy was not evident, Hoyeraal-Hreidarsson syndrome was suggested as a differential diagnosis. Instead of the conventional gene-specific approach with Sanger sequencing, we used whole-exome sequencing for the genetic diagnosis of this patient with possible Hoyeraal-Hreidarsson syndrome and successfully identified a missense mutation (c.146C>T, p.Thr49Me) in DKC1. CONCLUSION: This case suggests that whole-exome sequencing is particularly useful for the genetic diagnosis of extremely rare diseases with genetic heterogeneity, although there are many limitations, including cost and uneven or suboptimal coverage, to the application of this method as a routine genetic diagnosis.
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Authors | Byung Chan Lim, Seong-Keun Yoo, Seungbok Lee, Jong-Yeon Shin, Hee Hwang, Jong Hee Chae, Yong Seung Hwang, Jeong-Sun Seo, Jong-Il Kim, Ki Joong Kim |
Journal | Gene
(Gene)
Vol. 546
Issue 2
Pg. 425-9
(Aug 10 2014)
ISSN: 1879-0038 [Electronic] Netherlands |
PMID | 24914498
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier B.V. All rights reserved. |
Chemical References |
- Cell Cycle Proteins
- DKC1 protein, human
- Nuclear Proteins
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Topics |
- Adult
- Cell Cycle Proteins
(genetics)
- Child, Preschool
- DNA Mutational Analysis
- Diagnosis, Differential
- Dyskeratosis Congenita
(diagnosis, genetics, pathology)
- Exome
- Fetal Growth Retardation
(diagnosis, genetics, pathology)
- Humans
- Infant
- Intellectual Disability
(diagnosis, genetics, pathology)
- Male
- Microcephaly
(diagnosis, genetics, pathology)
- Mutation, Missense
- Nuclear Proteins
(genetics)
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