PDF(Pubmed)
Abstract：
UNASSIGNED: Upshaw-Schulman syndrome (USS) is rare, autosomal recessive, hereditary thrombotic thrombocytopenic purpura (TTP) caused by variants in a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13). USS has a heterogeneous clinical course, and most symptoms overlap with other diseases. Early diagnosis may have important implications for the patients. We found novel ADAMTS13 mutation and explored the clinical features and prognosis of newborn-onset USS to increase awareness of the disease.
UNASSIGNED: The same, non-consanguineous couple had three unexplained neonatal deaths. The symptoms of the three infants were mainly severe jaundice, anemia and thrombocytopenia after birth, which was consistent with the reported USS symptoms of neonates and died rapidly suddenly in the during rescue efforts. By using whole-exome sequencing (WES) for the study family, we found a novel heterozygous compound in ADAMTS13 (c.1187 (exon10) G>A (p.C396Y)/c.1595 (exon14) G>T (p.C532F)) that was carried by the three newborns originating from father and mother respectively. We reviewed nine published studies of newborn-onset USS and compared our cases for clinical symptoms and laboratory testing. All nine published cases were diagnosed by ADAMTS13 activity; in seven cases gene mutation analysis was performed and eight cases were still alive at the time of publication.
UNASSIGNED: The case has added clinicians\' awareness of the diagnosis and treatment of USS. A novel rare mutation in ADAMTS13 broadens the spectrum of genetic causes of this rare disorder and expands the phenotypic spectrum.
UNASSIGNED: The same, non-consanguineous couple had three unexplained neonatal deaths. The symptoms of the three infants were mainly severe jaundice, anemia and thrombocytopenia after birth, which was consistent with the reported USS symptoms of neonates and died rapidly suddenly in the during rescue efforts. By using whole-exome sequencing (WES) for the study family, we found a novel heterozygous compound in ADAMTS13 (c.1187 (exon10) G>A (p.C396Y)/c.1595 (exon14) G>T (p.C532F)) that was carried by the three newborns originating from father and mother respectively. We reviewed nine published studies of newborn-onset USS and compared our cases for clinical symptoms and laboratory testing. All nine published cases were diagnosed by ADAMTS13 activity; in seven cases gene mutation analysis was performed and eight cases were still alive at the time of publication.
UNASSIGNED: The case has added clinicians\' awareness of the diagnosis and treatment of USS. A novel rare mutation in ADAMTS13 broadens the spectrum of genetic causes of this rare disorder and expands the phenotypic spectrum.
摘要：
■Upshaw-Schulman综合征（USS）很少见，常染色体隐性遗传,遗传性血栓性血小板减少性紫癜（TTP）由具有血小板反应蛋白1型基序的解整合素样和金属蛋白酶变体（ADAMTS13）引起。USS有一个不同的临床过程，大多数症状与其他疾病重叠。早期诊断可能对患者有重要意义。我们发现了新的ADAMTS13突变，并探索了新生儿发病USS的临床特征和预后，以提高对该疾病的认识。
■相同，非近亲夫妇有3例原因不明的新生儿死亡。3名婴儿的症状主要是重度黄疸,出生后贫血和血小板减少症，这与报告的新生儿USS症状一致，并在抢救过程中迅速死亡。通过对研究家族使用全外显子组测序（WES），我们在ADAMTS13中发现了一个新的杂合化合物（c.1187（exon10）G>A（p。C396Y）/c.1595（exon14）G>T（p。C532F）），分别由父亲和母亲的三个新生儿携带。我们回顾了9项已发表的新生儿发作USS研究，并比较了我们的病例的临床症状和实验室检查。所有9例已发表的病例均通过ADAMTS13活性诊断；在7例中，进行了基因突变分析，8例在发表时仍存活。
■该病例增加了临床医生对USS的诊断和治疗的认识。ADAMTS13中的一种新的罕见突变拓宽了这种罕见疾病的遗传原因谱，并扩大了表型谱。
■相同，非近亲夫妇有3例原因不明的新生儿死亡。3名婴儿的症状主要是重度黄疸,出生后贫血和血小板减少症，这与报告的新生儿USS症状一致，并在抢救过程中迅速死亡。通过对研究家族使用全外显子组测序（WES），我们在ADAMTS13中发现了一个新的杂合化合物（c.1187（exon10）G>A（p。C396Y）/c.1595（exon14）G>T（p。C532F）），分别由父亲和母亲的三个新生儿携带。我们回顾了9项已发表的新生儿发作USS研究，并比较了我们的病例的临床症状和实验室检查。所有9例已发表的病例均通过ADAMTS13活性诊断；在7例中，进行了基因突变分析，8例在发表时仍存活。
■该病例增加了临床医生对USS的诊断和治疗的认识。ADAMTS13中的一种新的罕见突变拓宽了这种罕见疾病的遗传原因谱，并扩大了表型谱。
