Concomitant Upd(14)mat and Trisomy 14 Mosaicism in a Newborn Detected by Whole Genome Sequencing

Area of Science:

• Genetics
• Developmental Biology
• Pediatrics

Background:

• Temple syndrome (TS) is a rare imprinting disorder resulting from maternal uniparental disomy of chromosome 14 (upd(14)mat).
• TS is clinically characterized by growth retardation, hypotonia, developmental delay, and precocious puberty.
• The co-occurrence of upd(14)mat with trisomy 14 mosaicism is exceptionally rare, with limited reported cases.

Purpose of the Study:

• To report a novel case of a newborn with clinical features suggestive of TS.
• To investigate the underlying genetic cause, particularly focusing on uniparental disomy and chromosomal mosaicism.
• To underscore the importance of advanced genetic analyses in diagnosing rare imprinting disorders.

Main Methods:

• Trio whole genome sequencing (WGS) was performed on the patient and her parents.
• Bioinformatic analysis included standard variant detection and specialized pipelines for uniparental disomy (UPD) and low-level mosaicism detection.
• Clinical evaluation of the newborn included assessment of dysmorphic features, hypotonia, developmental delay, and cardiac malformations.

Main Results:

• Trio WGS initially revealed no causative sequence or structural variants.
• Further analysis using specialized pipelines identified maternal uniparental disomy of chromosome 14 (upd(14)mat).
• Low-level trisomy 14 mosaicism was also detected in the patient, indicating a complex chromosomal abnormality.

Conclusions:

• This case represents one of the few documented instances of upd(14)mat co-occurring with trisomy 14 mosaicism.
• Advanced genetic testing and meticulous data interpretation are crucial for diagnosing rare genetic disorders with complex mechanisms.
• Early and accurate diagnosis is vital for appropriate clinical management and genetic counseling in affected families.