| Autor: |
Reish, Orit, Huber, Céline, Altarescu, Gheona, ChapmanShimshoni, Daphne, LevyLahad, Ephrat, Renbaum, Paul, Mashevich, Maya, Munnich, Arnold, CormierDaire, Valérie |
| Zdroj: |
American Journal of Medical Genetics. Part A; September 2010, Vol. 152 Issue: 9 p2230-2235, 6p |
| Abstrakt: |
Mutations or deletions in the SHOXgene cause Leri–Weill dyschondrosteosis LWD and Langer mesomelic dysplasia LMD when present in heterozygous or homozygous form, respectively. A new class of enhancer deletions was identified 30–250 kb downstream of SHOX. We identified a female patient with marked short stature, mosaic for monosomy X in 31 of her lymphocytes, and findings consistent with LWD. Additional molecular studies demonstrated segregation of 17 polymorphic markers flanking and including the SHOXlocus, spanning 328 kb of pseudoautosomal region 1 PAR1 region. A deletion up to 10 kb residing 197 kb downstream of SHOXgene was detected, which was germinally transmitted from her clinically unaffected father. This was associated with postzygotic mosaic loss of the normal maternal Xchromosome, evidenced by fluorescent fragment analysis. Since most patients with LMD with deletions downstream of SHOXgene also have SHOXmutations in trans, it may suggest these deletions are associated with a milder phenotype. Further studies are required to elucidate the role of the former region in disease etiology. Mutations should be sought in clinically nonaffected family members because of the variable expressivity in hemizygous carriers, and cytogenetic evaluation should be considered to detect possible Xchromosome rearrangements underlying the haploinsufficiency for the PAR1 when deletion is detected by molecular analysis. Similarly, when LWD and marked short stature occur in a patient with mosaic Turner syndrome, the possibility of mutations in SHOXand the downstream of SHOXgene should be considered. © 2010 WileyLiss, Inc. |
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