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

Journal Article · · American Journal of Human Genetics
OSTI ID:133299
; ;  [1]
  1. Children`s Hospital of Philadelphia, PA (United States); and others

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.

OSTI ID:
133299
Report Number(s):
CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0026
Journal Information:
American Journal of Human Genetics, Vol. 55, 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