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.