Novel Hypomorphic Mutation in FANCD2 Gene Observed in a Fetus with Multiple Congenital Anomalies

Area of Science:

• Medical Genetics
• Developmental Biology
• Prenatal Diagnosis

Background:

• Congenital anomalies impact 1-2% of newborns, with significant variations affecting urinary tract, kidneys, and extremities.
• Prenatal diagnosis of fetal anomalies presents challenges for families and physicians, influencing prognosis and reproductive choices.
• Identifying the underlying genetic cause is crucial for understanding disease etiology and family counseling.

Purpose of the Study:

• To investigate the etiology of a severe fetal polymalformative syndrome detected prenatally.
• To highlight the utility of advanced genetic technologies in diagnosing rare monogenic disorders.
• To report a novel mutation in the FANCD2 gene associated with complex fetal anomalies.

Main Methods:

• Routine ultrasound at 24 weeks gestation revealed fetal growth retardation and multiple anomalies.
• Post-termination of pregnancy, SNP array genotyping and targeted gene next-generation sequencing (NGS) were employed.
• Analysis focused on identifying the genetic cause of the observed polymalformative syndrome.

Main Results:

• The fetus presented with growth retardation, unilateral kidney agenesis, bilateral upper-extremity malformations (radial bone and thumb absence), radial deviation, short humeri, nuchal fold thickening, and a single umbilical artery.
• SNP array and NGS identified a novel hypomorphic mutation in the FANCD2 gene.
• This mutation was determined to be the underlying cause of the severe fetal anomaly.

Conclusions:

• This case underscores the importance of advanced molecular techniques like SNP arrays and NGS in diagnosing rare genetic disorders.
• Identification of a novel FANCD2 mutation provides insight into the genetic basis of complex polymalformative syndromes.
• Accurate genetic diagnosis is essential for providing families with accurate prognoses and informed reproductive decision-making.