Father-to-daughter transmission of focal dermal hypoplasia associated with nonrandom X-inactivation: Support for X-linked inheritance and paternal X chromosome mosaicism
dc.contributor.author | Gorski, Jerome L. | en_US |
dc.date.accessioned | 2006-04-28T16:48:29Z | |
dc.date.available | 2006-04-28T16:48:29Z | |
dc.date.issued | 1991-09-01 | en_US |
dc.identifier.citation | Gorski, Jerome L. (1991)."Father-to-daughter transmission of focal dermal hypoplasia associated with nonrandom X-inactivation: Support for X-linked inheritance and paternal X chromosome mosaicism." American Journal of Medical Genetics 40(3): 332-337. <http://hdl.handle.net/2027.42/38255> | en_US |
dc.identifier.issn | 0148-7299 | en_US |
dc.identifier.issn | 1096-8628 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/38255 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=1951439&dopt=citation | en_US |
dc.description.abstract | Focal dermal hypoplasia (FDH) is a rare syndrome of severe developmental anomalies of the tissues and organs derived from ectoderm and mesoderm. Though data have suggested that FDH is an X-linked dominant trait associated with male hemizygote lethality, a hypothesis supported by the observation of three unrelated infants with FDH manifestations and de novo chromosome rearrangements involving Xp22, observations of father-to-daughter transmission have suggested possible genetic heterogeneity and autosomal dominant inheritance with sex limitation. We hypothesize that, if FDH is an X-linked disorder, cells expressing an active disease locus might experience a selective disadvantage resulting in a nonrandom pattern of X-inactivation in patient tissue. To test this hypothesis, we studied one of the two previously described families demonstrating father-to-daughter inheritance of FDH. To determine if the affected daughter had a skewed pattern of X-inactivation consistent with X-linked inheritance of FDH, somatic cell hybrids were constructed by fusing hypoxanthine phosphoribosyl transferase (HPRT)-deficient rodent fibro-blasts with either patient dermal fibroblasts or peripheral white blood cells (WBCs); hybrid clones retaining an active X chromosome were analyzed to determine the parental origin of the active X chromosome. Analyses of resulting hybrid clones showed that while hybrids constructed from skin fibroblasts contained an active X chromosome inherited from either of the patient's parents, hybrids constructed from WBCs showed a skewed pattern of X-inactivation; 11 of 11 hybrids contained an active maternal X chromosome (X 2 = 12.2, P = .001). These findings indicated that, in this family, FDH was associated with a nonrandom pattern of X-inactivation consistent with X-linked inheritance, suggesting that the patient's father was mosaic for a mutant FDH allele. | en_US |
dc.format.extent | 715148 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Genetics | en_US |
dc.title | Father-to-daughter transmission of focal dermal hypoplasia associated with nonrandom X-inactivation: Support for X-linked inheritance and paternal X chromosome mosaicism | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Genetics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Division of Pediatric Genetics, Departments of Pediatrics and Communicable Diseases and Human Genetics, University of Michigan Medical Center, Ann Arbor ; Division of Pediatric Genetics, 3570 MSRB II, 0688, University of Michigan, Ann Arbor, MI 48109–0688 | en_US |
dc.identifier.pmid | 1951439 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/38255/1/1320400317_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/ajmg.1320400317 | en_US |
dc.identifier.source | American Journal of Medical Genetics | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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