Refining the Clinical Spectrum of the 17p13.3 Microduplication Syndrome: Case-Report of a Familial Small Microduplication.

The chromosomal region 17p13.3 contains extensive repetitive sequences and is a well-recognized region of genomic instability. The 17p13.3 microduplication syndrome has been associated with a clinical spectrum of moderately non-specific phenotypes, including global developmental delay/intellectual disability, behavioral disorders, autism spectrum disorder and variable dysmorphic features. Depending on the genes involved in the microduplication, it can be categorized in two subtypes with different phenotypes. Here, we report a case of a 7-year-old boy with global developmental delay, speech impairment, hypotonia, behavioral conditions (ADHD and ODD), non-specific dysmorphic features and overgrowth. Genetic testing revealed a small 17p13.3 chromosomal duplication, which included the BHLHA9, CRK and YWHAE genes. Additionally, we observed that this was maternally inherited, and that the mother presented with a milder phenotype including mild learning disabilities, speech impairment and non-specific dysmorphic features, which did not significantly affect her. In conclusion, we present a clinical case of a 17p13.3 duplication that further delineates the clinical spectrum of this syndrome, including its intrafamilial/intergenerational variability.

Implementation of Exome Sequencing in Prenatal Diagnosis and Impact on Genetic Counseling: The Polish Experience.

BACKGROUND: Despite advances in routine prenatal cytogenetic testing, most anomalous fetuses remain without a genetic diagnosis. Exome sequencing (ES) is a molecular technique that identifies sequence variants across protein-coding regions and is now increasingly used in clinical practice. Fetal phenotypes differ from postnatal and, therefore, prenatal ES interpretation requires a large amount of data deriving from prenatal testing. The aim of our study was to present initial results of the implementation of ES to prenatal diagnosis in Polish patients and to discuss its possible clinical impact on genetic counseling. METHODS: In this study we performed a retrospective review of all fetal samples referred to our laboratory for ES from cooperating centers between January 2017 and June 2021. RESULTS: During the study period 122 fetuses were subjected to ES at our institution. There were 52 abnormal ES results: 31 in the group of fetuses with a single organ system anomaly and 21 in the group of fetuses with multisystem anomalies. The difference between groups was not statistically significant. There were 57 different pathogenic or likely pathogenic variants reported in 33 different genes. The most common were missense variants. In 17 cases the molecular diagnosis had an actual clinical impact on subsequent pregnancies or other family members. CONCLUSIONS: Exome sequencing increases the detection rate in fetuses with structural anomalies and improves genetic counseling for both the affected couple and their relatives.