Identification of a novel 15.5 kb SHOX deletion associated with marked intrafamilial phenotypic variability and analysis of its molecular origin
ANGELOS ALEXANDROU IOANNIS PAPAEVRIPIDOU KYRIAKOS TSANGARAS IOANNA ALEXANDROU MARIOS TRYFONIDIS VIOLETTA CHRISTOPHIDOU-ANASTASIADOU ELENI ZAMBA-PAPANICOLAOU GEORGE KOUMBARIS VASSOS NEOCLEOUS LEONIDAS A. PHYLACTOU NICOS SKORDIS GEORGE A. TANTELES CAROLINA SISMANI
Haploinsufficiency of the short stature homeobox contaning SHOX gene has been shown to result in a spectrum of phenotypes ranging from Leri–Weill dyschondrosteosis (LWD) at the more severe end to SHOX-related short stature at the milder end of the spectrum. Most alterations are whole gene deletions, point mutations within the coding region, or microdeletions in its flanking sequences. Here, we present the clinical and molecular data as well as the potential molecular mechanism underlying a novel microdeletion, causing a variable SHOX-related haploinsufficiency disorder in a three-generation family. The phenotyperesembles that of LWD in females, in males, however, the phenotypic expression is milder. The 15523-bp SHOX intragenic deletion, encompassing exons 3–6, was initially detected by array-CGH, followed by MLPA analysis. Sequencing of thebreakpoints indicated an Alu recombination-mediated deletion (ARMD) as the potential causative mechanism.
ANGELOS ALEXANDROU1 IOANNIS PAPAEVRIPIDOU1 KYRIAKOS TSANGARAS2 IOANNA ALEXANDROU1 MARIOS TRYFONIDIS3 VIOLETTA CHRISTOPHIDOU-ANASTASIADOU4 ELENI ZAMBA-PAPANICOLAOU5 GEORGE KOUMBARIS2 VASSOS NEOCLEOUS6 LEONIDAS A. PHYLACTOU6 NICOS SKORDIS7 GEORGE A. TANTELES4 CAROLINA SISMANI1
Volume 100, 2021
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