Clinical Phenotype and Genetic Analysis of a Family with 17q12 Microdeletion Syndrome

Abstract

ObjectiveTo clarify the genetic etiology of a 17q12 microdeletion syndrome fetus in a family and analyze the correlation between the genetic and clinical phenotypes within the family.MethodsA fetus with abnormal results from chromosomal microarray analysis (CMA) testing during the mother's prenatal checkup at Huzhou Maternal and Child Health Hospital in September 2020 was selected as the study subject. Clinical data of the fetus were collected, and the mother underwent amniocentesis. CMA was conducted on the fetus, and peripheral blood samples from the parents were collected for verification. After birth, the clinical phenotype of the child was systematically followed up in the pediatric health clinic.ResultsPrenatal ultrasound showed the fetus had bilateral kidney fullness with enhanced renal cortical echoes and polyhydramnios. CMA testing of the fetus revealed a 1.6 Mb heterozygous deletion in the 17q12 region, involving four OMIM pathogenic genes: HNF1B, ACACA, ZNHIT3, and PIGW. Her mother's CMA did not show any significant abnormalities, while her father carried a similar variation to that of the child, suggesting a paternal inheritance of the mutation. Based on the ACMG Guidelines for the Classification of Genetic Variants issued by the American College of Medical Genetics and Genomics, this variation was classified as pathogenic. After birth, the child exhibited mild hydronephrosis and epilepsy. Her father had left renal agenesis, multiple small crystals in the right kidney, mild right renal hydronephrosis, proteinuria, tubular urine, and mild liver dysfunction.ConclusionsThe child and her father, who share the same genetic variation, exhibit significant clinical heterogeneity.

Note:
Funding Information: This work was supported by grants from Huzhou Science and Technology Project of Zhejiang Province (No. 2022GYB54 to Y.L.)

Conflict of Interests: All of the authors had no any personal, financial, commercial, or academic conflicts of interest separately.

Ethical Approval: This study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of Huzhou Maternity and Child Health Care Hospital of Zhejiang Province (ethical batch number: 2021-J-117). Written informed consent was obtained from the patient.

Keywords: prenatal diagnosis, 17q12 microdeletion syndrome, Enhanced renal cortical echoes, Fetus