Prenatal diagnosis and molecular cytogenetic analyses of a rare 17q12 microdeletion and 17q11.2 microduplication family with normal phenotype.

BACKGROUND: Copy number variants (CNVs) are an important source of normal and pathogenic genome variations. Microdeletion of chromosome 17q12 results in structural or functional abnormalities in the kidney and urethra, type 5 diabetes (MODY5), and neurodevelopmental or neuropsychiatric disorders. Microduplication of 17q11.2 are less well-characterized but have been associated with variable clinical presentations, including autism spectrum disorder (ASD), developmental delay, and mild dysmorphic features.

CASE PRESENTATION: In this research, a 29-year-old woman (gravida 1, para 0) underwent amniocentesis at 22 weeks' gestation following the detection of bilateral hyperechogenic fetal kidneys on prenatal ultrasound. Notably, her husband has a medical history of congenital ichthyosis type 10, a genetic condition that warranted further genetic investigation.

RESULTS: Copy number variation sequencing (CNV-seq) from this family revealed a 1.46-Mb microdeletion on chromosome 17q12 and a 640-kb microduplication on chromosome 17q11.2 of the fetus, a 640-kb microduplication on chromosome 17q11.2 of the father. Trio whole-exome sequencing (WES) analysis revealed that the father carried compound heterozygous mutations in the pathogenic gene associated with congenital ichthyosis type 10, while the fetus was identified as a heterozygous carrier of one of these mutations.

CONCLUSION: We provide a detailed description of the phenotype in a rare family with 17q12 microdeletion, 17q11.2microduplication and congenital ichthyosis type 10. Combination of karyotype analysis, CNV-seq, WES, prenatal ultrasound and genetic counselling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications and pathogenic gene variants.