Kelkar Janhawi, DiMaio Miriam, Ma Deqiong, Zhang Hui
Division of Medical Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York, United States.
Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States.
Glob Med Genet. 2024 Mar 26;11(1):100-112. doi: 10.1055/s-0044-1785442. eCollection 2024 Jan.
We report a 4-year-old girl with neurodevelopmental abnormalities who has maternal uniparental isodisomy of chromosome 2 leading to homozygosity for a likely pathogenic variant in , and a variant of uncertain significance in . Biallelic pathogenic variants in lead to sepiapterin reductase deficiency (SRD), a dopa-responsive dystonia. Pathogenic variants in are associated with an autosomal recessive neurodevelopmental disorder characterized by impaired speech and hyperkinetic movements, which has significant clinical overlap with SRD. Our patient showed dramatic improvement in motor skills after treatment with levodopa. We also reviewed 67 published reports of uniparental disomy of chromosome 2 (UPD2) associated with various clinical outcomes. These include autosomal recessive disorders associated with loci on chromosome 2, infants with UPD2 whose gestations were associated with confined placental mosaicism for trisomy 2 leading to intrauterine growth restriction with good postnatal catchup growth, and normal phenotypes in children and adults with an incidental finding of either maternal or paternal UPD2. These latter reports provide support for the conclusion that genes located on chromosome 2 are not subject to imprinting. We also explore the mechanisms giving rise to UPD2.
我们报告了一名患有神经发育异常的4岁女孩，其母亲存在2号染色体单亲等臂双体，导致 中一个可能的致病变异纯合，以及 中一个意义未明的变异。 中的双等位基因致病变异导致蝶呤还原酶缺乏症（SRD），这是一种多巴反应性肌张力障碍。 中的致病变异与一种常染色体隐性神经发育障碍相关，其特征为言语受损和运动亢进，与SRD有显著的临床重叠。我们的患者在接受左旋多巴治疗后运动技能有显著改善。我们还回顾了67篇已发表的关于2号染色体单亲二体（UPD2）与各种临床结果相关的报告。这些包括与2号染色体上的基因座相关的常染色体隐性疾病、患有UPD2的婴儿，其妊娠与21三体局限胎盘嵌合体相关，导致宫内生长受限，但出生后追赶生长良好，以及偶然发现母源或父源UPD2的儿童和成人的正常表型。这些后者的报告支持了位于2号染色体上的基因不受印记影响这一结论。我们还探讨了产生UPD2的机制。
