Compound heterozygous protein C variants undetectable by common laboratory testing causing purpura fulminans after the neonatal period

2020 ◽  
Vol 95 (12) ◽  
pp. 1616-1621
Author(s):  
Kyle L. MacQuarrie ◽  
Olatundun Williams ◽  
Kenneth D. Friedman ◽  
Rachel S. Bercovitz
Keyword(s):  
Laboratory Testing ◽  
Protein C ◽  
Neonatal Period ◽  
Purpura Fulminans ◽  
Compound Heterozygous ◽  
Common Laboratory

A Compound Heterozygous Protein C Deficiency with a Single Nucleotide G Deletion Encoding Gly-381 and an Amino Acid Substitution of Lys for Gla-26

1993 ◽  
Vol 70 (04) ◽  
pp. 636-641 ◽  
Author(s):  
Masaru Ido ◽  
Michiaki Ohiwa ◽  
Tatsuya Hayashi ◽  
Junji Nishioka ◽  
Tsuyoshi Hatada ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein C ◽  
Purpura Fulminans ◽  
Male Infant ◽  
Compound Heterozygous ◽  
Dependent Manner ◽  
Protein C Deficiency ◽  
Single Nucleotide ◽  
Nucleotide Mutation ◽  
Gla Domain

SummaryWe report genetic abnormalities of protein C gene in a male infant who developed neonatal purpura fulminans. DNA-sequence analysis of all exons in protein C gene in this family revealed two mutations. The first abnormality, derived from the mother, was a deletion of one of four consecutive G at nucleotide number 10758 in exon IX which would result in a frame shift mutation and completely change amino acid sequence from Gly381 in the carboxyl-terminal region of protein C. The second abnormality, derived from the father, was a single nucleotide mutation from G to A in the codon (GAG to AAG) at nucleotide number 2977 in exon III, which would result in a substitution of Lys for γ-carboxyglutamic acid (Gla)26. This change would be responsible for the reduced immunological protein C levels of the patient and the father, estimated by a monoclonal antibody which recognizes the Gla-domain in a Ca2+-dependent manner (3.8% and 57%, respectively). Partially purified abnormal protein C from the father’s plasma showed a normal amidolytic activity and a change in the electrophoretic mobility. We detected the above mutations in his family members using two methods; one was a creation of new restriction enzyme sites using mutagenic primers and the other was single nucleotide primer extension. Both methods are rapid and useful for the diagnosis of prenatal protein C abnormalities.

A novel compound heterozygous mutations in protein C gene causing neonatal purpura fulminans

2018 ◽  
Vol 29 (2) ◽  
pp. 216-219 ◽  
Author(s):  
Huifei Zhang ◽  
Xiaojie Bi ◽  
Zhengxian Su ◽  
Xi Tu ◽  
Lizhen Wang ◽  
...  
Keyword(s):  
Protein C ◽  
Purpura Fulminans ◽  
Compound Heterozygous ◽  
Compound Heterozygous Mutations

scholarly journals A rare case of protein C mutation causing neonatal purpura fulminans

2021 ◽  
Author(s):  
Abdul Tawab ◽  
Madhu George ◽  
Jino Joseph ◽  
Ann Mary Zacharias
Keyword(s):  
Protein C ◽  
Autosomal Recessive ◽  
Purpura Fulminans ◽  
Rare Condition ◽  
Autosomal Recessive Inheritance ◽  
Fresh Frozen Plasma ◽  
Compound Heterozygous ◽  
Protein C Deficiency ◽  
Fresh Frozen ◽  
Proc Gene

Congenital protein C deficiency presenting as purpura fulminans is a rare condition in neonates. It is a disorder with autosomal recessive inheritance and is caused by homozygous or compound heterozygous mutations in PROC gene. The authors report a case of autosomal homozygous PROC gene transversion mutation in a newborn baby born to third degree consanguineous parents who presented as purpura fulminans at birth. She had almost undetectable protein C levels. As protein C concentrate was not readily available, she was managed with low molecular weight heparin along with fresh frozen plasma. Despite our best efforts, baby succumbed to her illness on day 21 of life.  Autosomal recessive protein C deficiency should always be sought as an explanation for thrombotic disorders in the newborn with manifestations of disseminated intravascular coagulation.

scholarly journals Genotypic and phenotypic character of Chinese neonates with congenital protein C deficiency: a case report and literature review

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Xiaoying Li ◽  
Xiaoyan Li ◽  
Xiao Li ◽  
Yuanhua Zhuang ◽  
Lili Kang ◽  
...  
Keyword(s):  
Literature Review ◽  
Protein C ◽  
Molecular Genetic ◽  
Purpura Fulminans ◽  
Protein S ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Molecular Testing ◽  
Compound Heterozygous ◽  
Protein C Deficiency

Abstract Background Our objective was to study the phenotype of and molecular genetic mechanisms underlying congenital protein C (PC) deficiency in Chinese neonates. We report the case of a neonate who presented 4 h after birth with purpura fulminans of the skin and thrombosis in the kidney. We also carried out a through literature review to study the genotype and phenotype, relevance, diagnosis, management, and prognosis of neonates with congenital PC deficiency in China. Case presentation and literature review Following a septic work-up and check of PC and protein S (PS) levels that showed PC deficiency, we investigated the patient’s and her parents’ genotypes. Our patient was found to have a plasma PC level of 0.8%. Molecular testing revealed a compound heterozygous mutation of the PROC gene: From the father, a c._262 G > T p. ASP88Tyr mutation in exon 4; from the mother, a C. 400 + 5G mutation in intron 5 that had been previously reported as likely pathogenic. Both parents were found to have heterozygous mutations for PC deficiency. In China, 5 other cases of congenital PC deficiency in the neonatal period were reported in the literature. In those cases, purpura fulminans and thrombosis were the main symptoms, and homozygous or compound heterozygous mutations of the PROC gene were identified. Conclusion Congenital PC deficiency should be ruled out for neonates presenting with purpura fulminans and thrombosis.

A novel compound heterozygous form of severe protein C deficiency causing bleeding without purpura fulminans

2017 ◽  
Vol 64 (11) ◽  
pp. e26626
Author(s):  
Nicole L. Herrick ◽  
Amy E. Geddis ◽  
Amy E. Lovejoy ◽  
Jenny Kim ◽  
Deborah Schiff ◽  
...  
Keyword(s):  
Protein C ◽  
Purpura Fulminans ◽  
Compound Heterozygous ◽  
Protein C Deficiency ◽  
Heterozygous Form

Purpura Fulminans in a Patient Homozygous for a Mutation in the Protein C Gene - Prenatal Diagnosis in a Subsequent Pregnancy

1996 ◽  
Vol 75 (03) ◽  
pp. 525-526 ◽  
Author(s):  
M C Alessi ◽  
M F Aillaud ◽  
O Paut ◽  
B Roquelaure ◽  
M Alhenc-Gelas ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Protein C ◽  
Purpura Fulminans ◽  
Subsequent Pregnancy

Prenatal Diagnosis of Compound Heterozygous Deficiency of Protein C by Direct Detection of the Mutation Sites

1996 ◽  
Vol 76 (02) ◽  
pp. 277-278 ◽  
Author(s):  
Masaru Ido ◽  
Tatsuya Hayashi ◽  
Junji Nishioka ◽  
Masazumi Itoh ◽  
Hiroyuki Minoura ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Protein C ◽  
Direct Detection ◽  
Compound Heterozygous ◽  
Heterozygous Deficiency

Severe Homozygous Protein C Deficiency: Identification of a Splice Site Missense Mutation (184, Q → H) in Exon 7 of the Protein C Gene

1994 ◽  
Vol 72 (01) ◽  
pp. 065-069 ◽  
Author(s):  
J M Soria ◽  
D Brito ◽  
J Barceló ◽  
J Fontcuberta ◽  
L Botero ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Gene Product ◽  
Splice Site ◽  
Protein C ◽  
Purpura Fulminans ◽  
Single Strand Conformation Polymorphism ◽  
Donor Splice Site ◽  
Protein C Deficiency ◽  
Donor Splice ◽  
Newborn Child

SummarySingle strand conformation polymorphism (SSCP) analysis of exon 7 of the protein C gene has identified a novel splice site missense mutation (184, Q → H), in a newborn child with purpura fulminans and undetectable protein C levels. The mutation, seen in the homozygous state in the child and in the heterozygous state in her mother, was characterized and found to be a G to C nucleotide substitution at the -1 position of the donor splice site of intron 7 of the protein C gene, which changes histidine 184 for glutamine (184, Q → H). According to analysis of the normal and mutated sequences, this mutation should also abolish the function of the donor splice site of intron 7 of the protein C gene. Since such a mutation is compatible with the absence of gene product in plasma and since DNA sequencing of all protein C gene exons in this patient did not reveal any other mutation, we postulate that mutation 184, Q → H results in the absence of protein C gene product in plasma, which could be the cause of the severe phenotype observed in this patient.

Purpura fulminans skin lesions in a newborn with complete protein C deficiency

1998 ◽  
Vol 132 (3) ◽  
pp. 558 ◽  
Author(s):  
Gideon Paret ◽  
Asher Barzilai ◽  
Zohar Barzilay
Keyword(s):  
Protein C ◽  
Purpura Fulminans ◽  
Skin Lesions ◽  
Protein C Deficiency ◽  
Complete Protein
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