Dempsey M A, Knight Johnson A E, Swope B S, Moldenhauer J S, Sroka H, Chong K, Chitayat D, Briere L, Lyon H, Palmer N, Gopalani S, Siebert J R, Lévesque S, Leblanc J, Menzies D, Haverfield E, Das S
Human Genetics, The University of Chicago, Chicago, IL, USA.
Prenat Diagn. 2014 Feb;34(2):163-7. doi: 10.1002/pd.4279. Epub 2013 Dec 9.
Cornelia de Lange syndrome (CdLS) is characterized by distinct facial features, growth retardation, upper limb reduction defects, hirsutism, and intellectual disability. NIPBL mutations have been identified in approximately 60% of patients with CdLS diagnosed postnatally. Prenatal ultrasound findings include upper limb reduction defects, intrauterine growth restriction, and micrognathia. CdLS has also been associated with decreased PAPP-A and increased nuchal translucency (NT). We reviewed NIPBL sequence analysis results for 12 prenatal samples in our laboratory to determine the frequency of mutations in our cohort.
This retrospective study analyzed data from all 12 prenatal cases with suspected CdLS, which were received by The University of Chicago Genetic Services Laboratories. Diagnostic NIPBL sequencing was performed for all samples. Clinical information was collected from referring physicians.
NIPBL mutations were identified in 9 out of the 12 cases prenatally (75%). Amongst the NIPBL mutation-positive cases with clinical information available, the most common findings were upper limb malformations and micrognathia. Five patients had NT measurements in the first trimester, of which four were noted to be increased.
We demonstrate that prenatally-detected phenotypes of CdLS, particularly severe micrognathia and bilateral upper limb defects, are associated with an increased frequency of NIPBL mutations.
科妮莉亚·德朗热综合征（CdLS）的特征为独特的面部特征、生长发育迟缓、上肢发育不全缺陷、多毛症和智力障碍。在出生后诊断的CdLS患者中，约60%已鉴定出NIPBL突变。产前超声检查结果包括上肢发育不全缺陷、宫内生长受限和小颌畸形。CdLS还与妊娠相关血浆蛋白-A降低和颈项透明层（NT）增厚有关。我们回顾了本实验室12份产前样本的NIPBL序列分析结果，以确定我们队列中的突变频率。
这项回顾性研究分析了芝加哥大学遗传服务实验室收到的所有12例疑似CdLS的产前病例的数据。对所有样本进行了NIPBL诊断性测序。从转诊医生处收集临床信息。
12例产前病例中有9例（75%）鉴定出NIPBL突变。在有临床信息的NIPBL突变阳性病例中，最常见的表现是上肢畸形和小颌畸形。5例患者在孕早期进行了NT测量，其中4例测量值升高。
我们证明，产前检测到的CdLS表型，特别是严重的小颌畸形和双侧上肢缺陷，与NIPBL突变频率增加有关。
