Clinical application of chromosomal microarray analysis for fetuses with craniofacial malformations

Area of Science:

• Genetics
• Prenatal Diagnosis
• Developmental Biology

Background:

• Chromosomal abnormalities pose challenges in diagnosing craniofacial malformations (CFMs) prenatally.
• Understanding the genetic basis of CFMs is crucial for accurate diagnosis and counseling.

Purpose of the Study:

• To evaluate chromosomal abnormalities in fetuses with CFMs using chromosomal microarray analysis (CMA) and G-banded chromosome analysis.
• To identify potential causative copy number variations (CNVs) and genes associated with CFMs.

Main Methods:

• Applied CMA and G-banded chromosome analysis to 118 fetuses with CFMs.
• Compared detection rates between isolated and non-isolated CFMs.
• Analyzed CNV/phenotype correlations to identify dosage-sensitive CFM genes.

Main Results:

• Non-isolated CFMs showed a significantly higher detection rate of chromosomal abnormalities (26/71) compared to isolated CFMs (7/47).
• CMA identified clinically significant findings in 28% (33/118) of fetuses, including aneuploidies, microdeletions/microduplications, and other CNVs.
• Identified potential causative genes for CFMs, such as TBX1, MAPK1, and SHH.

Conclusions:

• Findings enhance understanding of causative CNVs and genes in CFMs.
• Identifying the genetic basis of CFMs improves understanding of pathogenesis.
• Genetic insights facilitate more precise genetic counseling for affected families.