Evaluation of the possible association between higher than normal nuchal translucency with common mutations of SMN2 and PTPN11 genes in normal karyotype of pregnant women referred to Noor Comprehensive Genetics Center’s Clinic between 2019 and 2021

Nuchal translucency (NT), the ultrasound transparency detected behind the fetal neck, is considered a marker in the first trimester. Excessive increase in this marker is associated with chromosomal and structural abnormalities, as well as congenital birth defects, especially cardiovascular abnormalities. Noonan Syndrome and Spinal muscular atrophy (SMA) are two common associated syndromes with autosomal dominant and recessive inheritance respectively. PTPN11 is the most common gene whose mutation leads to Noonan syndrome. SMN2 gene is a modulating gene and in case of mutation, it leads to a benign increase in NT. The purpose of this article was to determine the causes for increased nuchal translucency in fetuses with normal karyotype by studying mutations in SMN2 and the two common exon 3 and exon 13 of PTPN11.

In this study, forty cases from Noor Genetics Clinics were entered. The cases were those who have both increased NT and normal karyotype. Amniotic fluid samples were acquired and DNA was extracted at the molecular laboratory. Then, genetic investigations were conducted using Real Time PCR and Sanger sequencing.

The investigation discovered four cases with deletion in SMN2; which none presented SMA pathogenesis. In one sample, Noonan syndrome pathogenesis through mutation in exon 13 was observed,  while no mutation in exon 3 was observed in any of the samples.

According to this study, it is suggested that molecular investigations, especially Noonan syndrome in fetuses with high NT level, should be included in the pregnancy screening program and diagnostic protocols in the society.