Genomic Profiling of Anophthalmia/Microphthalmia-Associated CNVs Reveals Complex Genotype-Phenotype Correlations and Incomplete Penetrance.
Dong Wu, Mengting Zhang, Qian Zhang et al.
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Case in brief
This case report discusses four families with anophthalmia/microphthalmia (A/M) and associated copy number variations (CNVs). Patient 1 had an inherited deletion that did not correlate with the phenotype, while Patients 2 and 3 had de novo pathogenic deletions affecting OTX2 and SOX2, leading to typical A/M. Case 4 presented a deletion involving OTX2 in a fetus and mother without ocular anomalies, highlighting the complexity of genotype-phenotype correlations.
Diagnostic / clinical pearl
Clinicians should be aware that CNV-induced haploinsufficiency can lead to significant phenotypic variability in anophthalmia/microphthalmia, necessitating careful interpretation of genetic findings.
Why it matters
Understanding the incomplete penetrance of genetic variants like OTX2 is crucial for accurate diagnosis and genetic counseling in families affected by ocular malformations.