Rapid Whole Genome Sequencing Uncovers a Triple Diagnosis: X-Linked Chondrodysplasia Punctata, MECP2-Related Disorder, and Mosaic Jacobs Syndrome

快速全基因组测序揭示三重诊断:X连锁点状软骨发育不良、MECP2相关疾病和嵌合型雅各布综合征

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Abstract

BACKGROUND: Rapid Whole Genome Sequencing (rWGS) is increasingly being used in neonatal intensive care units, as there is growing evidence that rare singe gene disorders present in the neonatal period and early identification can change management. While the diagnostic utility is increased with this broad testing, the possibility of unexpected findings also increases significantly. Here, we present a patient found to have three distinct genetic conditions through rWGS testing, with significant psychosocial and health consequences. METHODS AND RESULTS: This case report describes a patient who was identified with a form of chondrodysplasia punctata, as well as incidental findings of MECP2-related disorder and Jacobs' syndrome. To our knowledge, this is one of the first documented cases of triple genetic diagnoses in the literature, underscoring the expanding clinical utility of rWGS. CONCLUSION: Our patient represents a unique example of the utility of rWGS in the NICU setting. As two of the three conditions were unexpected results, his case is an important reminder of the possibility of unexpected findings for both providers and families. His case demonstrates the importance of pretest counseling and consenting processes, particularly in an acute setting. It also will add to our understanding of MECP2 variant presentations in males in the future.

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