Copy number variants at chromosome 17q12 including deletions and duplications have been associated with a spectrum of phenotypes. They are two distinct chromosomal aberrations. Deletions are well described and duplication is emerging as a new genetic syndrome. It has been reported that the estimated prevalence of patients with 17q12 deletion was 1.6 per 1,000,000 citizens, and the 17q12 duplication was 4.6 per 1,000,000 citizens in Denmark at the end of 2014. There was no other national prevalence data been reported. Recurrent genomic rearrangements of chromosome region 17q12, ranging from ~ 300 to ~ 2.1 Mb, have been described to be associated with a variable clinical phenotypes, including autism, behavioral abnormalities, facial dysmorphism, renal disease, joint laxity, esophageal atresia, anal atresia and endocrine abnormalitiesa. Neurological symptoms were the most common features associated with 17q12 duplications, including learning disability, seizures, and structural brain anomalies[7–15]. The incomplete penetrance rate was 21%.
Currently, all studies about 17q12 duplications are limited to phenotyped patients with 17q12 duplication or the family who was recruited through the identification of a duplication of 17q12 in the proband. There were no reports about prenatal screenings and diagnoses of 17q12 duplications. We analyzed the reason was that it was hard to find the fetal cases. At present, the detection techniques for fetal chromosome microdeletions and microduplications mainly include FISH and CMA. Because of the invasiveness and a 1%-3% risk of abortion, these techniques only be used as clinical diagnostic tools, not as clinical screening tools, and there are lots of strict restrictions before the amniocentesis, not just anyone who wants to do it.
As described above, different patients of the 17q12 duplication syndrome may have different phenotypes. Neurological symptoms (including learning disabilities, delayed language development and so on) were the most common features associated with 17q12 duplications, which means the ultrasound results usually would be normal during all the whole pregnancy period, and because of no obvious ultrasound indication, the patients are not allowed to perform the amniocentesis. So more effective methods of screening are needed for detecting the 17q12 duplication syndrome.
NIPT, as a new prenatal screening method, has many advantages, concluding a simple and noninvasive operation and a relatively easy quality control.NIPT is becoming more and more accepted by clinicians and patients. We have known that it is very efficient and accurate for the detection of common fetal chromosome aneuploidy, especially for chromosome 13, 18 and 21. Recently, some studies have found that NIPT through deeper sequencing can screen some microdeletions and microduplications, which are greater than 300 Kb in fetal genomes[18–22]. However, there are no reports of 17q12 duplication syndrome screened by NIPT previously.
In our study, we have successfully used NIPT to detect two patients with microduplications of about 2 Mb in fetal chromosome 17, then CMA was used to further pinpoint the specific duplication regions, confirming the results of NIPT. This chromosome 17q12 duplication syndrome would be missed if the two patients did not choose NIPT as their prenatal testing, which means NIPT maybe gave a clue for the possibility of chromosome abnormity.
Our cases indicated that NIPT was also useful as a clue to the chromosome microdeletions and microduplications.