Yang Xiangchun, Li Qiong, Wang Fei, Yan Lulu, Zhuang Danyan, Qiu Haiyan, Li Haibo, Chen Liang
The Central Laboratory of Birth Defects Prevention and Control, Ningbo Women and Children's Hospital, Ningbo, China.
Neonatal Screening Center, Ningbo Women and Children's Hospital, Ningbo, China.
Front Genet. 2021 Jun 24;12:686137. doi: 10.3389/fgene.2021.686137. eCollection 2021.
Primary carnitine deficiency (PCD) is an autosomal recessive disorder that could result in sudden death. It is caused by a defect in the carnitine transporter encoded by (Solute Carrier Family 22 Member 5, MIM:603377). Currently, a number of variants in have been identified, however, the PCD prevalence and its variants in Ningbo area are unclear. In this study, we screened 265,524 newborns by using tandem mass spectrometry. Variants in were further detected by next-generation sequencing in individuals with abnormal free carnitine levels (C0). We identified 53 newborns with abnormal C0 levels and 26 with variants in Among them, 16 with compound heterozygous or homozygous variants in were diagnosed with PCD, suggesting the PCD birth prevalence in Ningbo city was 1/16,595. Moreover, the C0 level was significantly ( = 0.013) higher in PCD patients than in those with one variant. Besides, the c.1400C > G (p. S467C) and c.51C > G (p. F17L) variants were the most frequent and six novel variants are all predicted to be damaging. This study reports the largest PCD patients in Ningbo area by newborn screening and expands the variant spectrum of . Our findings demonstrate the clinical value of combining NBS program results with DNA analysis for the diagnosis of PCD.
原发性肉碱缺乏症（PCD）是一种常染色体隐性疾病，可导致猝死。它由溶质载体家族22成员5（Solute Carrier Family 22 Member 5，MIM：603377）编码的肉碱转运体缺陷引起。目前，已在该基因中鉴定出许多变体，然而，宁波地区PCD的患病率及其变体尚不清楚。在本研究中，我们采用串联质谱法对265,524名新生儿进行了筛查。对游离肉碱水平（C0）异常的个体，通过二代测序进一步检测该基因的变体。我们鉴定出53名C0水平异常的新生儿，其中26名该基因存在变体。其中，16名该基因存在复合杂合或纯合变体的新生儿被诊断为PCD，这表明宁波市PCD的出生患病率为1/16,595。此外，PCD患者的C0水平显著高于（P = 0.013）仅携带一个变体的患者。此外，c.1400C > G（p.S467C）和c.51C > G（p.F17L）变体最为常见，并且六个新变体均预测具有损害性。本研究通过新生儿筛查报告了宁波地区最大规模的PCD患者群体，并扩展了该基因的变体谱。我们的研究结果证明了将新生儿筛查结果与DNA分析相结合用于PCD诊断的临床价值。
