Introduction
Peripheral blood is typically the preferred specimen for initial genetic evaluation because of its reliable, high-quality DNA yield. However, in recent years buccal swabs have become increasingly preferred due to their convenience and ease of collection. Laboratories have observed that buccal swab samples seem to have higher diagnostic yield than blood specimens for detection of mosaicism by chromosomal microarray analysis (CMA) and next generation sequencing (NGS) assays. We present a case where Prader-Willi syndrome (PWS) was not initially detected by CMA on a blood specimen, but subsequent exome sequencing (ES) on a buccal specimen detected a mosaic deletion of 15q11.1q12, confirming the PWS diagnosis.  PWS is caused by paternal inheritance of large deletions in the 15q11-15q13 region, aberrant imprinting or gene silencing with variable phenotypes based on the type of disruption. PWS is characterized by hypotonia, intellectual disability, developmental delay, motor delay, dysmorphic features, sleep apnea, and hypogonadism among other symptoms. 

Case Presentation
A 29-day old male born preterm at 33wk4d presented with respiratory distress, dysmorphic features, hypotonia and undescended testis.  

Diagnostic Workup
PWS was suspected, and so CMA and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) for the PWS critical region were performed on a blood sample. While MS-MLPA was negative, CMA identified a deletion of 15q12q13.1, which was classified as a variant of uncertain significance not linked to PWS. By age 4, the proband continued to have delayed milestones and a phenotype resembling PWS, and so ES was ordered using a buccal swab specimen. ES revealed a mosaic deletion of 15q11.1q12, corresponding to the PWS critical region. The discrepancy between the CMA and ES results were suspected to be related to tissue-limited mosaicism, and so CMA was repeated using a buccal swab specimen. This time, CMA detected both the previously observed 15q12q13.1 deletion seen in the blood sample, as well as the mosaic deletion of 15q11.1q12 seen in by ES on the buccal sample.   

Treatment and Management
 With a confirmed diagnosis, the proband is now undergoing speech therapy, physiotherapy, diet management, and surgery for obstructive sleep apnea and undescended testis.

Outcome and Follow-Up
N/A

Discussion
This case underscores the challenges of detecting tissue-limited mosaicism and the importance of re-testing a different specimen while exhausting genetic testing modalities, especially when there is a strong clinical suspicion. While buccal swabs are cost effective and a convenient mode of sampling, they also have advantages over blood specimens for detection of mosaic variants. This is likely due to the range of cell types present in saliva such as leukocytes, cells of mesodermal and ectodermal origin, and fibroblast cells. Buccal samples have also been widely used in NGS assays, and higher detection rates of mosaic variants over blood samples has been well documented.

Conclusion
In this rare case, we found a mosaic copy number variant only in the buccal sample, which helped to diagnose PWS. Thus, while blood is a preferred source of DNA for most genetic assays, certain conditions, such as tissue-limited mosaicism, may necessitate testing alternative samples to ensure an accurate diagnosis.