Gouas Laetitia, Kémény Stéphan, Beaufrère Anne-Marie, Eymard-Pierre Eléonore, Pebrel-Richard Céline, Tchirkov Andrei, Lemery Didier, Laurichesse-Delmas Hélène, Vago Philippe, Goumy Carole
Service de Cytogx00E9;nx00E9;tique Mx00E9;dicale, Unitx00E9; de Mx00E9;decine Fx0153;tale, CHU Clermont-Ferrand, Clermont-Ferrand, France.
Cytogenet Genome Res. 2015;146(1):28-32. doi: 10.1159/000435865. Epub 2015 Jul 21.
Fetuses with increased nuchal translucency thickness (NT) are at increased risk for chromosomal abnormalities. In case of a normal karyotype, a minority of them may present with structural abnormalities or genetic syndromes, which may be related to submicroscopic chromosomal imbalances. The objective of this study was to evaluate whether MLPA screening of 21 syndromic and subtelomeric regions could improve the detection rate of small chromosomal aberrations in fetuses with increased NT and a normal karyotype. A total of 106 prenatal samples from fetuses with NT ≥ 99th centile and normal R- and G-banding were analyzed by MLPA for subtelomeric imbalances (SALSA P036 and P070) and 21 syndromic regions (SALSA P245). One sample showed a benign CNV (dup(8)pter, FBXO25 gene), and 1 patient was found to have a loss of 18 qter and a gain of 5 pter as a result of an unbalanced translocation. The incidence of cryptic pathogenic variants was <1% or 2.7% when only fetuses with other ultrasound abnormalities were taken into account. Submicroscopic imbalances in fetuses with increased NT may be individually rare, and genome-wide screening seems more likely to improve the diagnostic yield in these fetuses.
颈部半透明层厚度（NT）增加的胎儿染色体异常风险增加。在核型正常的情况下，其中少数可能存在结构异常或遗传综合征，这可能与亚微观染色体失衡有关。本研究的目的是评估对21个综合征性和亚端粒区域进行多重连接依赖探针扩增（MLPA）筛查是否能提高NT增加且核型正常的胎儿中小染色体畸变的检出率。对106例NT≥第99百分位数且R和G带正常的胎儿的产前样本进行MLPA分析，以检测亚端粒失衡（SALSA P036和P070）和21个综合征区域（SALSA P245）。1个样本显示良性拷贝数变异（dup(8)pter，FBXO25基因），1例患者因不平衡易位导致18号染色体长臂末端缺失和5号染色体短臂末端增加。仅考虑有其他超声异常的胎儿时，隐匿性致病变异的发生率<1%或2.7%。NT增加的胎儿中的亚微观失衡可能个体罕见，全基因组筛查似乎更有可能提高这些胎儿的诊断率。
