Prenatal diagnosis and follow-up of a child with mosaic tetrasomy 9p without obvious abnormal clinical manifestations

INTRODUCTION: To report the prenatal diagnosis and follow-up of a fetus with mosaic tetrasomy 9p without obvious abnormal clinical manifestations. CASE REPORT: A fetus diagnosed with mosaic T9p at Shaoxing Maternal and Child Health Hospital in February 2022 was selected as the study subject. The amniotic fluid karyotype was 47,XY,+i(9)(p10)[3]/46,XY[97]. CNV-seq revealed a 70.56 Mb copy number gain in 9p24.3q21.11 (mosaicism at 6%). After genetic counseling, the parents opted to continue the pregnancy. A 3.9 kg male fetus was delivered at full term with normal physical findings at birth. The baby was phenotypically normal and had normal psychomotor and language development at 3 years old, at our last postnatal follow-up. When the child was 3 years old, his physical measurement parameters (height: 97 cm; weight: 14 kg) and neurodevelopment milestones all met the age standards. His peripheral blood karyotype was 47,XY,+i(9)(p10)[10]/46,XY[90], with CNV-seq analysis indicating a 39.16 Mb copy number gain in the 9p24.3p13.1 region (mosaicism at 53%). This discrepancy with the amniotic fluid CNV-seq results was attributed to differences in segmentation algorithms or software. FISH detected T9p mosaicism in oral mucosa (11.2%) and urinary sediment cells (12.7%). A synthesis of data from karyotype analysis, CNV-seq, and FISH collectively substantiates the presence of an acquired alteration within the 9p region, while the evidence does not support the extension of this fragment across the centromere of chromosome 9 into the q arm. CONCLUSION: The combined use of various methods may be capable of more accurately determining break-points and mosaic levels of T9p during prenatal diagnosis. This enriches the clinical spectrum of T9p mosaicism and provides a basis for prenatal diagnosis and genetic counseling of children with this type of chromosome variation.