背景：我们报道了一对受Noonan综合征（NS）影响的双胎双胎（DCDA）妊娠，通过遗传分析确定了LZTR1的新突变。
方法：一名妊娠12+2周时有单卵双胞胎（DCDA）的孕妇被转诊到我们的中心。这是她在先前分娩健康婴儿后的第二次怀孕。两个胎儿的颈部半透明性分别为11.2mm（CRL62.0mm）和6.9mm（CRL62.1mm）。超声检查提示：囊性水瘤，耳部发育不良。这对夫妇没有血缘关系,两者均具有正常表型。家族性遗传性疾病也被排除。在超声引导下,获得30毫克绒毛膜绒毛进行核型分析，定量荧光聚合酶链反应(QF-PCR),染色体微阵列分析（CMA），和三全外显子组测序（WES）检查。我们使用了“目标区域捕获和测序”来进行WES，以及用于数据分析的BWA（BurrowsWheelerAligner）Multi-Vision软件包。所有这些测试的结果都是正常的，除了WES在这对双胞胎中检测到LZTR1基因外显子区的c.427A>G突变和与NS相关的p。Asn143Asp新杂合突变。此外,WES表明，双胞胎胎儿的突变起源于母亲。当母亲拿到基因检测报告时，她来到我们的胎儿医学部门进行遗传咨询，但她拒绝了临床遗传学家的任命。这对夫妇选择终止妊娠。因为患者没有选择在我们医院终止妊娠，我们无法参加进一步的考试。在另一家医院同事的帮助下，拍了胎儿的照片。与产前超声检查结果相比，“囊性水瘤”和“发育不良的耳朵”的出现与超声检查一致。这对夫妇在知道这一致病结果后感到沮丧，尽管我们建议母亲进一步调查，他们拒绝了。
结论：突变位点可能是不完全显性的，导致胎儿表型异常，如囊性水瘤和发育不良的耳朵。
BACKGROUND: We report a pair of dichorionic diamniotic (DCDA) twin pregnancy affected by Noonan syndrome (NS) with a novel mutation of LZTR1 determined by genetic analysis.
METHODS: A pregnant woman with monozygotic twins (DCDA) at 12 + 2 weeks gestation was referred to our center. This was her second pregnancy following a previous delivery of a healthy infant. Nuchal translucency of two fetuses was 11.2 mm (CRL 62.0 mm) and 6.9 mm (CRL 62.1 mm) respectively. Ultrasound examination indicated cystic hygroma and hypoplastic ear. The couple was not consanguineous, and both had normal phenotype. Familial hereditary disease was also excluded. Under ultrasound guidance, 30 mg of chorionic villi was obtained for karyotyping, quantitative fluorescent polymerase chain reaction (QF-PCR), chromosomal microarray analysis(CMA), and Trio-whole-exome sequencing(WES) examination. We used the \"target region capture and sequencing\" for WES, and the BWA (Burrows Wheeler Aligner) Multi-Vision software package for the data analysis. The results of all these tests were normal except WES detected a c.427 A > G mutation in the exonic region of the LZTR1 gene and a p. Asn143Asp novel heterozygous mutation associated with NS in this pair of twins. In addition, WES suggested that the mutation in the twin fetuses originated from the mother. When the mother got the genetic test report, she came to our fetal medicine department for genetic counseling and she declined the appointment with a clinical geneticist. The couple opted to terminate the pregnancy. Because the patient did not choose to terminate the pregnancy at our hospital, we were unable to take further examination. With the help of colleagues in another hospital, photos of the fetuses were taken. Compared with the prenatal ultrasound results, the appearance of the \"cystic hygroma\" and \"hypoplastic ear\" was consistent with the ultrasound. The couple were depressed after knowing this pathogenic result and although we advised the mother to take further investigation, they refused.
CONCLUSIONS: The mutant locus might be incompletely dominant, which led to an abnormal fetal phenotype such as cystic hygroma and hypoplastic ear.
