A Study of Congenital Protein C Deficiency With Infancy Onset of CADASIL in a Chinese Baby

Abstract

Objective: The main objectives of this article were to study a severe congenital protein C deficiency (PCD) in a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and analyze the cause of this case.

Materials and methods: We had recorded clinical manifestations of the patient, laboratory tests, imaging studies, and gene sequencing of the PROC gene and NOTCH3 gene to study the disease in this family. We checked the change of NOTCH3 protein by immunohistochemistry.

Results: Laboratory studies of the patient had revealed that his PC activity was 3%. Magnetic resonance imaging results showed hyperintense lesions in the cerebral white matter of the patient. PROC gene and NOTCH3 gene sequencing was performed among the family members. The patient was confirmed as homozygous for the (A-G)-12 at the transcription initiation site in the promoter region of the PROC gene and heterozygous mutation of the NOTCH3 gene. Immunohistochemical results showed that NOTCH3 protein was positive in the skin vascular smooth muscle of the patient.

Conclusions: We studied a rare case of an infat boy diagnosed with both congenital PCD and CADASIL; congenital PCD was attributable to a compound that was homozygous for (A-G)-12 at the transcription initiation site in the promoter region of the PROC gene, and CADASIL was caused by missense mutation in exon 24 of NOTCH3. He was a sporadic patient with congenital PCD and CADASIL; it maybe that the deficiency of protein C led to early onset of CADASIL. The gene sequencing of PROC gene and NOTCH3 gene may have important value for fertility guidance and prenatal diagnosis.

FIGURE 1

A, The pedigree of the family with protein C deficiency. The index patient was indicated with an arrow. B, Results of PROC gene sequencing for this family. *indicates the mutation location in this sequencing report.

FIGURE 2

A, Magnetic resonance imaging scan of the brain showing multiple hyperintense centrum ovale white matter lesions on T2-weigthed images. B, Magnetic resonance imaging scan of the brain showing multiple hyperintense periventricular white matter lesions on T2-weighted images. C, Mother's magnetic resonance imaging scan of the brain showing multiple hyperintense centrum ovale white matter lesions on T2-weigthed images. D, Mother's magnetic resonance imaging scan of the brain showing multiple hyperintense periventricular white matter lesions on T2-weighted images.

FIGURE 3

A, The pedigree of the family with NOTCH3 protien. The index patient was indicated with an arrow. B, Results of NOTCH3 gene sequencing for this family.

FIGURE 4

Immunohistochemistry of NOTCH3 protein with skin tissue. Immunohistochemistry data showed the NOTCH3 protein was positive in the patient’s skin vascular smooth muscle (scar, ×200).