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The First Hospital of LanZhou University

The first hospital of LanZhou University and Genemind collaborated in a publication on BMC Medical Genomics, titled “Fraternal twins with Phelan-McDermid syndrome not involving the SHANK3 gene: case report and literature review”. This study demonstrated a comprehensive analysis of Phelan-McDermid syndrome case based on DNA sequencing data from the GenoCare platform.

The case involves one pair of twins with intellectual disability and speech absence. Initial genetic testing with tandem mass spectroscopy and karyotype analysis did not yield remarkable result. CNV-seq analysis of the two patients revealed a heterozygous deletion at the 22q13.31-22q13.33 region. The deletion sizes were 6.36Mb and 6.34 Mb. They are diagnosed as Phelan-McDermid syndrome.

Phelan-McDermid syndrome, also referred to as 22q13 deletion syndrome, is a rare genetic disorder caused by deletion of distal long arm of chromosome 22 with a variety of clinical feature. This syndrome is characterized by global developmental delay, intellectual disability, absent or severely delayed speech, hypotonia, minor dysmorphic features and autism. The SHANK3 gene is understood to be the critical gene for the neurological features of this syndrome.

In order to further confirm the diagnosis, the authors performed single-molecule sequencing (GenoCare 1600) on samples from the two patients and their parents. The result showed that the two patients’ deletions were identical; with breakpoints at 44850001 bp and 50,850,001 bp (GRCh37/hg19). Carrier testing in the parents revealed normal results in the 22q13.31-q13.33 region, indicating a de novo 22q13.31-q13.33 deletion in their children (Fig. 2). The hemizygous region included 45 protein-coding genes not involving the SHANK3 gene.

Compared to traditional methods such as karyotype analysis and chromosomal microarray analysis (CMA), single molecule sequencing with GenoCare 1600 delivered more accurate results. In this study, the two patients’ chromosome anomaly came from germline mosaicism, which is challenging to detect with non-sequencing method. In our earlier publication, we have showed that single molecule sequencing can detect as low as 20% of such mosaicism events. Therefore, with single molecule sequencing, we could enable prenatal diagnosis that detects many chromosome anomalies early.