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Title: Classical Wolf-Hirschhorn Syndrome confirmed molecularly despite normal results using commercially available probes: Redefinition of critical region

Abstract

Wolf-Hirschhorn Syndrome, WHS, (4p-) is a clinically recognized entity where the deletion ranges from one half of the short arm of 4p to being subtle and cytogenetically undetectable. Because such variations do not result in significant differences in the WMS phenotype it has been suggested that them is a critical region involved in the distal portion of chromosome 4, within 4p16.3. This has been recently localized to a 2.5 Mb segment 100-300 kb from the telomere. A cosmid probe, pC847.351, that maps to distal 4p16.3 (locus D4F26) is commercially available for diagnostic use. We present a child with classical feature of Wolf-Hirschhorn Syndrome whose chromosome analyses, including high resolution banding, looking specifically at the 4p region, were normal, and in whom FISH using the commercially available cosmid probe for the 4p16.3 region did not demonstrate a deletion. Insistence on the clinician`s part that the child`s features were classic for WHS prompted further investigation. Four additional cosmid clones distal to the HD gene were tested by FISH on metaphase chromosomes from the proband. Cosmids representing the loci D4S95 and D4S43, which are {approximately}3.5 and 2.5 Mb, Respectively, proximal to D4F26 were present. However, cosmids for the loci D4S98 and FGFR3, whichmore » are within 100 kb of each other and {approximately}300 kb distal to D4S43 were deleted. This deletion is the smallest reported to date in a patient with typical WHS. Previous studies of patients both lacking the WHS phenotype and deleted using cosmid probe pC847.351 have suggested that the most distal region (150 kb) of 4p16.3 is not part of the WHS critical region. This is confirmed by our study. Estabrooks` report, together with our case, suggests redefinition of the WHS critical region proximal to D4F26 and distal to D4S43. We caution against ruling out WHS with the above probe since there may be other cases where the most distal region is intact.« less

Authors:
; ;  [1]
  1. Children`s Hospital of Philadelphia, PA (United States); and others
Publication Date:
OSTI Identifier:
133299
Report Number(s):
CONF-941009-
Journal ID: AJHGAG; ISSN 0002-9297; TRN: 95:005313-0026
Resource Type:
Journal Article
Journal Name:
American Journal of Human Genetics
Additional Journal Information:
Journal Volume: 55; Journal Issue: Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; PATIENTS; HEREDITARY DISEASES; MENTAL DISORDERS; NERVOUS SYSTEM DISEASES; HUMAN CHROMOSOMES; GENETIC MAPPING; CHROMOSOMAL ABERRATIONS; GENE MUTATIONS; DETECTION; GENES; BIOLOGICAL MARKERS; POLYMERASE CHAIN REACTION; TELOMERES; PHENOTYPE; DNA HYBRIDIZATION; FLUORESCENCE; BANDING TECHNIQUES

Citation Formats

Zackai, E H, McDonald-McGinn, D M, and Spinner, N. Classical Wolf-Hirschhorn Syndrome confirmed molecularly despite normal results using commercially available probes: Redefinition of critical region. United States: N. p., 1994. Web.
Zackai, E H, McDonald-McGinn, D M, & Spinner, N. Classical Wolf-Hirschhorn Syndrome confirmed molecularly despite normal results using commercially available probes: Redefinition of critical region. United States.
Zackai, E H, McDonald-McGinn, D M, and Spinner, N. 1994. "Classical Wolf-Hirschhorn Syndrome confirmed molecularly despite normal results using commercially available probes: Redefinition of critical region". United States.
@article{osti_133299,
title = {Classical Wolf-Hirschhorn Syndrome confirmed molecularly despite normal results using commercially available probes: Redefinition of critical region},
author = {Zackai, E H and McDonald-McGinn, D M and Spinner, N},
abstractNote = {Wolf-Hirschhorn Syndrome, WHS, (4p-) is a clinically recognized entity where the deletion ranges from one half of the short arm of 4p to being subtle and cytogenetically undetectable. Because such variations do not result in significant differences in the WMS phenotype it has been suggested that them is a critical region involved in the distal portion of chromosome 4, within 4p16.3. This has been recently localized to a 2.5 Mb segment 100-300 kb from the telomere. A cosmid probe, pC847.351, that maps to distal 4p16.3 (locus D4F26) is commercially available for diagnostic use. We present a child with classical feature of Wolf-Hirschhorn Syndrome whose chromosome analyses, including high resolution banding, looking specifically at the 4p region, were normal, and in whom FISH using the commercially available cosmid probe for the 4p16.3 region did not demonstrate a deletion. Insistence on the clinician`s part that the child`s features were classic for WHS prompted further investigation. Four additional cosmid clones distal to the HD gene were tested by FISH on metaphase chromosomes from the proband. Cosmids representing the loci D4S95 and D4S43, which are {approximately}3.5 and 2.5 Mb, Respectively, proximal to D4F26 were present. However, cosmids for the loci D4S98 and FGFR3, which are within 100 kb of each other and {approximately}300 kb distal to D4S43 were deleted. This deletion is the smallest reported to date in a patient with typical WHS. Previous studies of patients both lacking the WHS phenotype and deleted using cosmid probe pC847.351 have suggested that the most distal region (150 kb) of 4p16.3 is not part of the WHS critical region. This is confirmed by our study. Estabrooks` report, together with our case, suggests redefinition of the WHS critical region proximal to D4F26 and distal to D4S43. We caution against ruling out WHS with the above probe since there may be other cases where the most distal region is intact.},
doi = {},
url = {https://www.osti.gov/biblio/133299}, journal = {American Journal of Human Genetics},
number = Suppl.3,
volume = 55,
place = {United States},
year = {Thu Sep 01 00:00:00 EDT 1994},
month = {Thu Sep 01 00:00:00 EDT 1994}
}