TY - JOUR
T1 - Identification of a novel 15.5 kb SHOX deletion associated with marked intrafamilial phenotypic variability and analysis of its molecular origin
AU - Alexandrou, Angelos
AU - Papaevripidou, Ioannis
AU - Tsangaras, Kyriakos
AU - Alexandrou, Ioanna
AU - Tryfonidis, Marios
AU - Christophidou-Anastasiadou, Violetta
AU - Zamba-Papanicolaou, Eleni
AU - Koumbaris, George
AU - Neocleous, Vassos
AU - Phylactou, Leonidas A.
AU - Skordis, Nicos
AU - Tanteles, George A.
AU - Sismani, Carolina
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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 phenotype resembles 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 the breakpoints indicated an Alu recombination-mediated deletion (ARMD) as the potential causative mechanism.
AB - 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 phenotype resembles 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 the breakpoints indicated an Alu recombination-mediated deletion (ARMD) as the potential causative mechanism.
KW - ARMD
KW - haploinsufficiency
KW - intragenic deletion
KW - Leri–Weill syndrome
KW - SHOX gene
UR - http://www.scopus.com/inward/record.url?scp=84992741108&partnerID=8YFLogxK
U2 - 10.1007/s12041-016-0698-y
DO - 10.1007/s12041-016-0698-y
M3 - Article
C2 - 27994182
AN - SCOPUS:84992741108
SN - 0022-1333
VL - 95
SP - 839
EP - 845
JO - Journal of Genetics
JF - Journal of Genetics
IS - 4
ER -