背景:耳廓髁突综合征(ARCND)是一种罕见的先天性第一和第二咽弓的颅面发育畸形综合征,在肺叶和螺旋之间的连接处出现外耳畸形,上颌畸形,下颌髁突发育不全。到目前为止,已经描述了ARCND的四种亚型,也就是说,ARCND1(OMIM#602483),ARCND2(ARCND2A,OMIM#614669;ARCND2B,OMIM#620458),ARCND3(OMIM#615706),和ARCND4(OMIM#620457)。
方法:本研究报告了一例由PLCB4基因中的一种新的致病变异导致的ARCND2,并总结了PLCB4基因突变位点和ARCND2的表型。
结果:先证者,一个5天大的男性新生儿,因呼吸窘迫被转诊到我们医院.小颌畸形,微小口腔,独特的问号耳朵,以及下颌髁突发育不全。基于三重奏的全外显子组测序鉴定了NM_001377142.1:c.1928C>T的新型错义变体(NP_001364071.1:p。Ser643Phe)在PLCB4基因中,预测会损害局部结构稳定性,结果可能会影响蛋白质的功能。从文献回顾来看,仅检索到36例PLCB4基因突变患者.
结论:与其他检查ARCND2家族性病例的研究一样,在PLCB4基因的不同家族杂合突变中观察到不完全外显率和可变表达率。虽然,绝大多数ARCND2患者的运动和智力发育在正常范围内,仍需长期随访和评估.
BACKGROUND: Auriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear malformation at the junction between the lobe and helix, micromaxillary malformation, and mandibular condylar hypoplasia. Four subtypes of ARCND have been described so far, that is, ARCND1 (OMIM # 602483), ARCND2 (ARCND2A, OMIM # 614669; ARCND2B, OMIM # 620458), ARCND3 (OMIM # 615706), and ARCND4 (OMIM # 620457).
METHODS: This study reports a case of ARCND2 resulting from a novel pathogenic variant in the PLCB4 gene, and summarizes PLCB4 gene mutation sites and phenotypes of ARCND2.
RESULTS: The proband, a 5-day-old male neonate, was referred to our hospital for respiratory distress. Micrognathia, microstomia, distinctive question mark ears, as well as mandibular condyle hypoplasia were identified. Trio-based whole-exome sequencing identified a novel missense variant of NM_001377142.1:c.1928C>T (NP_001364071.1:p.Ser643Phe) in the PLCB4 gene, which was predicted to impair the local structural stability with a result that the protein function might be affected. From a review of the literature, only 36 patients with PLCB4 gene mutations were retrieved.
CONCLUSIONS: As with other studies examining familial cases of ARCND2, incomplete penetrance and variable expressivity were observed within different families\' heterozygous mutations in PLCB4 gene. Although, motor and intellectual development are in the normal range in the vast majority of patients with ARCND2, long-term follow-up and assessment are still required.