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Abstract：
BACKGROUND: Maternal uniparental disomy for chromosome 6 (upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat) has been previously reported to cause intrauterine growth restriction (IUGR), but the specific clinical phenotype has not been defined. Based on clinical data from two new cases and patients from the literature, specific phenotypes and mechanisms will be discussed further.
METHODS: In case 1, a maternal isodisomy mixed with a heterodisomy was found on chromosome 6, including a regional absence of heterozygosity between 6q23.3 and 6q27. In case 2, a homozygous SCUBE3 mutation and upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat, involving the 6p21.1-25.1 region were found. Clinical data related to upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat were also reviewed. Of all the 21 reported cases with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat (including our 2 cases), 18 (85.7%) presented IUGR.
CONCLUSIONS: The phenotypes of the two newly identified patients with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat further suggest that IUGR is associated with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and case 2 is the first reported upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat patient with a homozygous SCUBE3 gene mutation. However, the specific phenotypes involved in upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and the related mechanisms need to be further studied.
METHODS: In case 1, a maternal isodisomy mixed with a heterodisomy was found on chromosome 6, including a regional absence of heterozygosity between 6q23.3 and 6q27. In case 2, a homozygous SCUBE3 mutation and upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat, involving the 6p21.1-25.1 region were found. Clinical data related to upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat were also reviewed. Of all the 21 reported cases with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat (including our 2 cases), 18 (85.7%) presented IUGR.
CONCLUSIONS: The phenotypes of the two newly identified patients with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat further suggest that IUGR is associated with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and case 2 is the first reported upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat patient with a homozygous SCUBE3 gene mutation. However, the specific phenotypes involved in upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and the related mechanisms need to be further studied.
摘要：
背景：6号染色体的母本单亲二体性（CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。)mat)之前曾报道过导致宫内生长受限(IUGR)，但具体的临床表型尚未明确。根据两个新病例的临床数据和文献中的患者，具体的表型和机制将进一步讨论。
方法：在病例1中，在6号染色体上发现了混合有异体性的母体同体性，包括6q23.3和6q27之间的区域杂合性缺失。在病例2中，纯合SCUBE3突变和upd(CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。)mat,发现涉及6p21.1-25.1区域。与upd相关的临床数据(CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。)垫子也被审查了。在所有21例报告的upd病例中（CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。)垫子(包括我们的2箱)，18（85.7%）呈现IUGR。
结论：两名新发现的upd患者的表型（CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。)mat进一步表明IUGR与upd(CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。)mat和案例2是第一个报告的upd(CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。）患有纯合SCUBE3基因突变的患者。然而,UPD涉及的特定表型(CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。)垫和相关机理需要进一步研究。
方法：在病例1中，在6号染色体上发现了混合有异体性的母体同体性，包括6q23.3和6q27之间的区域杂合性缺失。在病例2中，纯合SCUBE3突变和upd(CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。)mat,发现涉及6p21.1-25.1区域。与upd相关的临床数据(CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。)垫子也被审查了。在所有21例报告的upd病例中（CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。)垫子(包括我们的2箱)，18（85.7%）呈现IUGR。
结论：两名新发现的upd患者的表型（CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。)mat进一步表明IUGR与upd(CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。)mat和案例2是第一个报告的upd(CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。）患有纯合SCUBE3基因突变的患者。然而,UPD涉及的特定表型(CajaibaMM，WitchelS,Madan-KhetarpalS,胡佛·J,HoffnerL,MacphersonT,etal.产前诊断6三体解救导致父系UPD6具有新的胎盘发现。美国医学杂志A.2011；155A（8）：1996-2002。)垫和相关机理需要进一步研究。
