The 18q12.3 region contains the SET binding protein 1 (SETBP1) gene. SETBP1 mutations or deletions are associated with Schinzel-Giedion syndrome or intellectual developmental disorder, autosomal dominant 29. We report the prenatal diagnosis and genetic counseling of a patient with a maternally inherited 18q12.3 microdeletion. In this family, the mother and son carried the same microdeletion. Chromosomal microdeletions and microduplications are difficult to detect using conventional cytogenetics, whereas the combination of prenatal ultrasound, karyotype analysis, chromosomal microarray analysis, and genetic counseling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications.

Copy number variations (CNVs) in chromosome 16p11.2 (deletions and duplications) are not rare. 16p11.2 microdeletion is among the most commonly known genetic etiologies of autism spectrum disorder, overweightness, and related neurodevelopmental disorders. Here, we report the prenatal diagnosis and genetic counseling of a maternally inherited 16p11.2 microdeletion. In this family, the mother and fetus both have a normal phenotype and the same microdeletion. Following the use of molecular genetic techniques, including array-based methods, the number of reported cases has rapidly increased. The combination of prenatal ultrasound, karyotype analysis, chromosomal microarray analysis (CMA), and genetic counseling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications.

OBJECTIVE: To investigate the mutations in patients with Axenfeld-Rieger syndrome (ARS) and the pattern of PITX2-related tooth agenesis.
METHODS: Whole-exome sequencing (WES) and copy number variation (CNV) array were used to screen the mutations in four ARS probands. After Sanger sequencing and quantitative polymerase chain reaction (qPCR) validation, secondary structure prediction and dual-luciferase assay were employed to investigate the functional impact. Eighteen PITX2-mutated patients with definite dental records were retrieved from our database and literatures, and the pattern of PITX2-related tooth agenesis was analyzed.
RESULTS: A novel de novo segmental deletion of chromosome 4q25 (GRCh37/hg19 chr4:111, 320, 052-111, 754, 236) encompassing PITX2 and three novel PITX2 mutations c.148C > T, c.257G > A, and c.630insCG were identified. Preliminary functional studies indicated the transactivation capacity of mutant PITX2 on Distal-less homeobox 2 (DLX2) promoter was compromised. The maxillary teeth showed significantly higher rate of agenesis (57.94%) than the mandibular teeth (44.05%). The most often missing teeth were upper lateral incisors (83.33%) and upper second premolars (69.44%). Teeth with the least agenesis rate were the lower second molars (19.44%) and lower first molars (8.33%).
CONCLUSIONS: We identified a novel 4q25 microdeletion including PITX2 and three novel PITX2 mutations, and statistically analyzed the PITX2-related tooth agenesis pattern.