摘要目的:探讨2例 FAM111A基因变异所致细长骨发育不良(OCS)胎儿的产前表型及遗传学特征。 方法:选取2例因产前超声提示"胎儿肢体测量值小于孕周、颅骨形态不规整"等异常于2021年4月和8月在沧州市人民医院接受产前诊断的胎儿为研究对象，整理并分析其临床及影像学资料。采集胎儿羊水以及孕妇夫妇的外周血样进行核心家系全外显子组测序(trio-WES)，并通过Sanger测序对候选变异进行家系验证。以" FAM111A基因""细长骨发育不良"" FAM111A""osteocraniostenosis"等为关键词，检索中国知网、万方数据知识服务平台和PubMed数据库2000年1月1日至2025年6月30日期间收录的文献。本研究通过了本院医学伦理委员会的审查(批准号：K2020-049)。 结果:胎儿1表现为四肢短小、颅骨形态异常及脑沟回表浅等；胎儿2表现为四肢短小、颅骨光环不规则、前额突出及双额变窄等。Trio-WES显示胎儿1携带 FAM111A基因c.1582G>C(p.Asp528His)杂合错义变异，查询人群数据库中未见收录，亦未见文献报道。胎儿2携带 FAM111A基因c.1020_1022delTTC(p.Ser343del)杂合框内缺失变异，分别被ClinVar和HGMD数据库收录为可能致病性与致病性变异。两对夫妇Sanger测序均未携带相同的变异。文献检索共发现4篇报道、涉及9例患儿，主要特征包括宫内生长受限、颅骨骨化不良、长骨纤细及髓腔狭窄、面容异常等，与本研究2例胎儿的宫内发育迟缓、颅骨矿化不足及长骨纤细等表型大体相符。 结论:确诊了2例OCS的胎儿，发现1处新的 FAM111A错义变异和1处已知可能致病的框内缺失，丰富了OCS的表型谱，为后续的产前诊断和遗传咨询提供了依据。

abstractsObjective:To investigate the prenatal manifestation and genetic basis for two fetuses suspected for Osteocraniostenosis (OCS).Methods:Two fetuses undergoing invasive prenatal diagnosis at Cangzhou People′s Hospital in April and August 2021 for short long bones and abnormal skull morphology were selected as the study subjects. Clinical data were collected and analyzed. Genomic DNA was extracted from amniotic fluid and peripheral blood samples of the two couples. Candidate variants were validated by Sanger sequencing. Literature was retrieved from CNKI, Wanfang Data Knowledge Service Platform and PubMed using keywords including " FAM111A gene", " gracile bone dysplasia", " FAM111A" and " osteocraniostenosis" from January 1, 2000 to June 30, 2025. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K2020-049). Results:Fetus 1 was found to have short limbs, abnormal skull morphology and shallow cerebral sulci. Fetus 2 showed short limbs, irregular skull halo, prominent forehead and bilateral frontal narrowing. Trio-WES revealed that fetus 1 has carried a heterozygous missense variant c. 1582G>C (p.Asp528His) in exon 4 of the FAM111A gene, which was unreported previously. Fetus 2 has harbored a heterozygous in-frame deletion c. 1020_1022delTTC (p.Ser343del) in exon 6 of the FAM111A gene, which has been recorded as likely pathogenic by the ClinVar and HGMD databases. Sanger sequencing confirmed that the parents of both fetuses were wild-type for the variant sites. A total of 9 previously reported patients with FAM111A-related gracile bone dysplasia/OCS from 4 publications were retrieved. The main clinical features included intrauterine growth restriction, hypomineralized skull, gracile long bones with narrow medullary cavities and characteristic facial anomalies, which were in large in keeping with the prenatal features of the two fetuses. Conclusion:Both fetuses were diagnosed with FAM111A-related OCS based on the characteristic prenatal findings and identification of the FAM111A variants. Above finding expanded the phenotypic spectrum of FAM111A-associated disorders and provided clues for the prenatal diagnosis and genetic counseling.