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| MOLECULAR ANALYSIS OF THE SMITH-MAGENIS SYNDROME - A POSSIBLE CONTIGUOUS-GENE SYNDROME ASSOCIATED WITH DEL(17)(P11.2) |
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| Author(s): GREENBERG F, GUZZETTA V, DEOCALUNA RM, MAGENIS RE, SMITH ACM, RICHTER SF, KONDO I, DOBYNS WB, PATEL PI, LUPSKI JR |
| Source: AMERICAN JOURNAL OF HUMAN GENETICS Volume: 49 Issue: 6 Pages: 1207-1218 Published: DEC 1991 |
| Times Cited: 162 References: 47 |
| Abstract: We undertook clinical evaluation (32 cases) and molecular evaluation (31 cases) of unrelated patients affected with Smith-Magenis syndrome (SMS) associated with an interstitial deletion of band p11.2 of chromosome 17. Patients were evaluated both clinically and electrophysiologically for peripheral neuropathy, since markers showing close linkage to one form of Charcot-Marie-Tooth disease (CMT1A) map to this chromosomal region. The common clinical findings were broad flat midface with brachycephaly, broad nasal bridge, brachydactyly, speech delay, and hoarse, deep voice. Fifty-five percent of the patients showed clinical signs (e.g., decreased or absent deep tendon reflexes, pes planus or pes cavus, decreased sensitivity to pain, and decreased leg muscle mass) suggestive of peripheral neuropathy. However, unlike patients with CMT1A, these patients demonstrated normal nerve conduction velocities. Self-destructive behaviors, primarily onychotillomania and polyembolokoilamania, were observed in 67% of the patients, and significant symptoms of sleep disturbance were observed in 62%. The absence of REM sleep was demonstrated by polysomnography in two patients. Southern analysis indicated that most patients were deleted for five 17p11.2 markers - FG1 (D17S446), 1516 (D17S258), pYNM67-R5 (D17S29), pA10-41 (D17S71), and pS6.1-HN2 (D17S445) - thus defining a region which appears to be critical to SMS. The deletion was determined to be of paternal origin in nine patients and of maternal origin in six patients. The apparent random parental origin of deletion documented in 15 patients suggests that genomic imprinting does not play a role in the expression of the SMS clinical phenotype. Our findings suggest that SMS is likely a contiguous-gene deletion syndrome which comprises characteristic clinical features, developmental delay, clinical signs of peripheral neuropathy, abnormal sleep function, and specific behavioral anomalies. |
| Document Type: Article |
| Language: English |
| Reprint Address: LUPSKI, JR (reprint author), BAYLOR COLL MED, INST MOLEC GENET, 1 BAYLOR PLAZA, T-905, HOUSTON, TX 77030 USA |
Addresses:
1. BAYLOR COLL MED, INST MOLEC GENET, 1 BAYLOR PLAZA, T-905, HOUSTON, TX 77030 USA
2. BAYLOR COLL MED, CTR HUMAN GENOME, HOUSTON, TX 77030 USA
3. BAYLOR COLL MED, DEPT PEDIAT, HOUSTON, TX 77030 USA
4. BAYLOR COLL MED, TEXAS CHILDRENS HOSP, HOUSTON, TX 77030 USA
5. OREGON HLTH SCI UNIV, DEPT MOLEC GENET, PORTLAND, OR 97201 USA
6. OREGON HLTH SCI UNIV, CHILD DEV REHABIL CTR, PORTLAND, OR 97201 USA
7. CHILDRENS HOSP, DENVER, CO 80218 USA
8. UNIV ARIZONA, DEPT PEDIAT, TUCSON, AZ 85721 USA
9. UNIV RYUKYUS, DEPT HUMAN ECOL & GENET, NAHA, OKINAWA 903 JAPAN
10. INDIANA UNIV, SCH MED, DEPT NEUROL, INDIANAPOLIS, IN 46202 USA
11. INDIANA UNIV, SCH MED, DEPT MOLEC GENET, INDIANAPOLIS, IN 46202 USA |
| Publisher: UNIV CHICAGO PRESS, 5720 S WOODLAWN AVE, CHICAGO, IL 60637 |
| Subject Category: Genetics & Heredity |
| IDS Number: GU672 |
| ISSN: 0002-9297 |
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