下面附上的是microarray 的报告。现在我们在等我俩的基因测试结果，最希望这个问 题是遗传的（我俩家里都没有类似的问题）。 主要的风险是developmental delay, autism, or congenital anomalies。我觉得有些风险我们可以承担，但是如果是严重 的autism，intellectural disorder是我们没法承受的。同时，如果因为轻微可以忽视的问题而终结一胎导致危及另一胎，我们也没有办法接受。请问你们对这个报告中提到的风险看法如何？末尾提到的『 Clinical correlation is required』是什么意思？
Unclear male result with an interstitial duplication within 13q21.32 of uncertain clinical significance. Within this ~1 Mb 13q21.32 region, there is only a partial duplication of one protein-coding gene, PCDH9, and several non-protein-coding genes. PCDH9 encodes a neuronal protocadherin relevant to cell adhesion. Deletions in PCDH9 have been proposed to be a potential risk factor for autism spectrum disorder (Marshall et al, 2008). However, there are no proposed effects of partial duplication of this gene, as in this case. A large case-control study did not demonstrate a statistically significant enrichment of copy gains involving PCDH9 in affected patients versus controls (Cooper et al, 2011). Similar duplications have been identified postnatally in the ClinGen and DECIPHER databases and classified as either likely benign (1 case) or uncertain significance (6 cases), with a most common phenotype of developmental delay. However, given ascertainment bias in these databases (i.e. the large majority of patients included in these databases have a presentation including development delay), this finding does not constitute a reliable genotype-phenotype correlation.
This variant primarily meets our prenatal reporting criteria as it exceeds the size of 1 Mb. In general, the size of this duplication raises suspicion for possible clinical relevance, as copy number variants of this size are generally seen in ~2% of the normal population but ~15% of patients affected by developmental delay, autism, or congenital anomalies (Cooper et al, 2011). However, the lack of any clear effect of PCDH9 partial copy gain, and the fact it is a duplication, which is less likely to carry phenotypic effects than a deletion (Rosenfeld et al, 2013), both argue against any particular clinical relevance. Based on a recent population-based study, the finding of a relatively large copy number variant, such as this one, may best be considered a potential risk factor for possible neurodevelopmental or educational effects (Mannik et al, 2015),, but there is also a high likelihood this variant will carry no phenotypic effects at all. Parental studies may be informative in this case: if this copy number variant is inherited from an unaffected parent, it further decreases any likelihood of clinical relevance postnatally. However, given the well-characterized possibility of variable phenotypic penetrance of copy number variants ( Rosenfeld et al, 2013), even inheritance from a normal parent does not rule out any potential postnatal effect. Unfortunately, we do not have any additional testing modalities which can definitely predict whether this copy number variant is a benign change or carries any clinical relevance.
GUIDANCE FOR NEXT STEPS: 1. Parental analyses could be considered to clarify whether this copy number change was de novo or inherited from a carrier parent. 2. Genetic counseling is recommended. 3. Clinical correlation is required
医生建议做近一步检查。我们做了CVS，确定没有唐氏，高兴了几天，接着 microarray 结果出来，发现染色体13有microduplication，属于 VOUS(不确定).胎儿现在已经16
周了，做selective reduction危及健康的孩子的风险非常大。我读了论坛里所有相关
的讨论，CMA report 也通读了几遍，但是还希望能
得到一些专业人士的建议。
下面附上的是microarray 的报告。现在我们在等我俩的基因测试结果，最希望这个问
题是遗传的（我俩家里都没有类似的问题）。 主要的风险是developmental delay,
autism, or congenital anomalies。我觉得有些风险我们可以承担，但是如果是严重
的autism，intellectural disorder是我们没法承受的。同时，如果因为轻微可以忽视的问题而终结一胎导致危及另一胎，我们也没有办法接受。请问你们对这个报告中提到的风险看法如何？末尾提到的『 Clinical correlation is required』是什么意思？
Unclear male result with an interstitial duplication within 13q21.32 of
uncertain clinical significance. Within this ~1 Mb 13q21.32 region, there is only a partial duplication of one protein-coding gene, PCDH9, and several
non-protein-coding genes. PCDH9 encodes a neuronal protocadherin relevant to cell adhesion. Deletions in PCDH9 have been proposed to be a potential risk factor for autism spectrum disorder (Marshall et al, 2008). However, there are no proposed effects of partial duplication of this gene, as in this case. A large case-control study did not demonstrate a statistically significant enrichment of copy gains involving PCDH9 in affected patients versus
controls (Cooper et al, 2011). Similar duplications have been identified
postnatally in the ClinGen and DECIPHER databases and classified as either
likely benign (1 case) or uncertain significance (6 cases), with a most
common phenotype of developmental delay. However, given ascertainment bias
in these databases (i.e. the large majority of patients included in these
databases have a presentation including development delay), this finding
does not constitute a reliable genotype-phenotype correlation.
This variant primarily meets our prenatal reporting criteria as it exceeds
the size of 1 Mb. In general, the size of this duplication raises suspicion for possible clinical relevance, as copy number variants of this size are
generally seen in ~2% of the normal population but ~15% of patients affected by developmental delay, autism, or congenital anomalies (Cooper et al, 2011). However, the lack of any clear effect of PCDH9 partial copy gain, and the fact it is a duplication, which is less likely to carry phenotypic effects than a deletion (Rosenfeld et al, 2013), both argue against any particular
clinical relevance. Based on a recent population-based study, the finding of a relatively large copy number variant, such as this one, may best be
considered a potential risk factor for possible neurodevelopmental or
educational effects (Mannik et al, 2015),, but there is also a high
likelihood this variant will carry no phenotypic effects at all. Parental
studies may be informative in this case: if this copy number variant is
inherited from an unaffected parent, it further decreases any likelihood of clinical relevance postnatally. However, given the well-characterized
possibility of variable phenotypic penetrance of copy number variants (
Rosenfeld et al, 2013), even inheritance from a normal parent does not rule out any potential postnatal effect. Unfortunately, we do not have any
additional testing modalities which can definitely predict whether this copy number variant is a benign change or carries any clinical relevance.
Unclear finding: 13q21.32 Copy Gain
Genomic Coordinates: 66,213,704 - 67,220,803
Estimated Size: 1.007 Mb
Number of Probes: 320 Probes
Significance: Uncertain clinical significance
Inheritance: Unknown
Genes: HNRNPA3P5, LINC01052, MIR548X2, MIR4704, TRIM60P19, PCDH9, PCDH9-AS1, RNU7-87P.
GUIDANCE FOR NEXT STEPS:
1. Parental analyses could be considered to clarify whether this copy number change was de novo or inherited from a carrier parent.
2. Genetic counseling is recommended.
3. Clinical correlation is required
2. 染色体异常多数都不是遗传的，这跟遗传病是两回事
3. 你们为啥先做CVS再做microarray
4. 你们医生说啥？
uncertain，你问别人也问不出来什么
CVS是绒毛活检吧？查了一下绒毛膜取样比羊膜穿刺风险还高，但羊膜穿刺准确率更高。
另外，现在无创产检已经可以做到很灵敏很准确了，风险又小，可以试一下。请阅读这个知乎的链接：https://www.zhihu.com/question/29570937
最后，想说几句，妈妈的心理生理状态对胎儿的影响挺大的，现在爸爸以泪洗面就算了，妈妈最好能更坚强一些。最后很有可能确诊宝宝是健康无恙的呢，那么现在的担心就是瞎操心了呢。
真心祝福一切都好~
即使有阳性，往往也要羊穿来确定
已经16周了，羊穿可能费效比比较高
看下database, DGV 或者https://gene.sfari.org/autdb/CNVSecDis.do?l=13q21.32
然后cvs又正常。。。
说明这类检查都很不可靠么？
祝福lz
microduplication这种东西，真是很难说。很多newborn的rare disease都是这个导致
的。功能搞不清楚