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Down syndrome phenotypes: the consequences of chromosomal imbalance
Korenberg JR, Chen XN, Schipper R, Sun Z, Gonsky R, Gerwehr S, Carpenter N, Daumer C et al.. Proceedings of the National Academy of Sciences of the United States of America, 1994-05-01
Topic: Brain proteins, microglia and lab models
Down syndrome (DS) is a major cause of mental retardation and congenital heart disease. Besides a characteristic set of facial and physical features, DS is associated with congenital anomalies of the gastrointestinal tract, an increased risk of leukemia, immune system defects, and an Alzheimer-like dementia. Moreover, DS is a model for the study of human aneuploidy. Although usually caused by the presence of an extra chromosome 21, subsets of the phenotypic features of DS may be caused by the duplication of small regions of the chromosome. The physical map of chromosome 21 allows the molecular definition of the regions duplicated in these rare cases of partial trisomy. As a first step in identifying the genes responsible for individual DS features and their pathophysiology, a panel of cell lines derived from 16 such individuals has been established and the molecular break points have been determined using fluorescence in situ hybridization and Southern blot dosage analysis of 32 markers unique to human chromosome 21. Combining this information with detailed clinical evaluations of these patients, we have now constructed a "phenotypic map" that includes 25 features and assigns regions of 2-20 megabases as likely to contain the genes responsible. This study provides evidence for a significant contribution of genes outside the D21S55 region to the DS phenotypes, including the facies, microcephaly, short stature, hypotonia, abnormal dermatoglyphics, and mental retardation. This strongly suggests DS is a contiguous gene syndrome and augurs against a single DS chromosomal region responsible for most of the DS phenotypic features.
Key findings
- Besides a characteristic set of facial and physical features, DS is associated with congenital anomalies of the gastrointestinal tract, an increased risk of leukemia, immune system defects, and an Alzheimer-like dementia.
- This study provides evidence for a significant contribution of genes outside the D21S55 region to the DS phenotypes, including the facies, microcephaly, short stature, hypotonia, abnormal dermatoglyphics, and mental retardation.
Why it matters
This study used cell lines from people with partial trisomy 21 to build a phenotypic map assigning regions of chromosome 21 to features of Down syndrome, including an Alzheimer-like dementia. It is genetic mapping work and reports no treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 1994 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 790 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 23.2 citations a year over 34 year(s) since 1994 |
| Impact for its field and year | 5 / 6 | Cited 38.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 15 other studies in this library |
| Still being cited | 2 / 4 | Cited 35 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Christine M. Distèche: h-index 79 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8197171) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Korenberg, JR., Chen, X. N., Schipper, R., Sun, Z., Gonsky, R., Gerwehr, S., et al. (1994). Down syndrome phenotypes: the consequences of chromosomal imbalance. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.91.11.4997
Vancouver
Korenberg JR, Chen XN, Schipper R, Sun Z, Gonsky R, Gerwehr S, et al. Down syndrome phenotypes: the consequences of chromosomal imbalance. Proceedings of the National Academy of Sciences of the United States of America. 1994. doi:10.1073/pnas.91.11.4997. PMID: 8197171.
BibTeX
@article{korenberg1994-8197171,
author = {Korenberg, JR. and Chen, X. N. and Schipper, R. and Sun, Z. and Gonsky, R. and Gerwehr, S. and Carpenter, N. and Daumer, C. and others},
title = {{Down syndrome phenotypes: the consequences of chromosomal imbalance}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {1994},
doi = {10.1073/pnas.91.11.4997},
pmid = {8197171},
url = {https://doi.org/10.1073/pnas.91.11.4997}
}
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