背景：小于胎龄（SGA）的病因是多因素的，包括母体/子宫-胎盘因素，胎儿表观遗传学,和遗传异常。我们评估了无已知原因的SGA婴儿中靶向组测序（TES）或全外显子组测序（WES）的遗传原因和诊断有效性。
方法：对2019年1月至2020年12月在釜山国立大学医院出生体重小于胎龄10百分位数的新生儿进行了一项前瞻性研究。我们排除了已知SGA原因的婴儿，包括母体原因或主要的先天性异常或感染。没有已知病因的SGA婴儿接受了遗传评估，包括核型分析,染色体微阵列（CMA），和TES/WES。
结果：在研究期间，82名SGA婴儿在我们医院出生。其中,61例患者被排除在外。共有21例患者接受了核型分析和染色体CMA，在两名患者中检测到像差，包括一个染色体异常和一个拷贝数变异。19例染色体核型和CMA检查结果正常的患者接受了TES或WES，确定了三个致病或可能致病的单基因突变，即LHX3、TLK2和MED13L。
结论：在没有已知危险因素的SGA婴儿中，遗传原因的患病率为22％（5/21）。在核型和CMA正常的SGA婴儿中，TES或WES的诊断率为15.7％（3/19）。TES或WES对确定无已知原因的SGA婴儿的病因非常有帮助。
BACKGROUND: The etiology of small for gestational age (SGA) is multifactorial and includes maternal/uterine-placental factors, fetal epigenetics, and genetic abnormalities. We evaluated the genetic causes and diagnostic effectiveness of targeted-panel sequencing (TES) or whole-exome sequencing (WES) in SGA infants without a known cause.
METHODS: A prospective
study was conducted on newborn infants born with a birth weight of less than the 10th percentile for gestational age between January 2019 and December 2020 at the Pusan National University Hospital. We excluded infants with known causes of SGA, including maternal causes or major congenital anomalies or infections. SGA infants without a known etiology underwent genetic evaluation, including karyotyping, chromosomal microarray (CMA), and TES/WES.
RESULTS: During the
study period, 82 SGA infants were born at our hospital. Among them, 61 patients were excluded. A total of 21 patients underwent karyotyping and chromosomal CMA, and aberrations were detected in two patients, including one chromosomal anomaly and one copy number variation. Nineteen patients with normal karyotype and CMA findings underwent TES or WES, which identified three pathogenic or likely pathogenic single-gene mutations, namely LHX3, TLK2, and MED13L.
CONCLUSIONS: In SGA infants without known risk factors, the prevalence of genetic causes was 22% (5/21). The diagnostic yield of TES or WES in SGA infants with normal karyotype and CMA was 15.7% (3/19). TES or WES was quite helpful in identifying the etiology in SGA infants without a known cause.
