NEMO Gene Mutations in Two Chinese Females with Incontinentia Pigmenti

Abstract

Purpose: To identify the mutations of the NEMO gene in two Chinese females with incontinentia pigmenti.

Patients and methods: Patients were both from Nanchong, Sichuan Province. Genomic DNA was extracted from the peripheral blood of patients and patient 1's father. The mutations of the NEMO gene in patient 1 by GAP polymerase chain reaction and Sanger sequencing and her father were detected. NEMO-specific polymerase chain reaction and Sanger sequencing were used to identify the NEMO gene mutation in patient 2.

Results: DNA analysis identified a rare frameshift mutation, c.723_c.724insCAGG(p.A242QfsX15) in exon 5 of the NEMO gene in patient 1 with a family history but not in her healthy father. The common deletion of exons 4-10 of the NEMO gene was found in sporadic patient 2.

Conclusion: Our data revealed that the rare frameshift mutation, c.723_c.724insCAGG(p.A242QfsX15) in exon 5 of the NEMO gene in patient 1 and the deletion of exons 4-10 of the NEMO gene in patient 2 could cause the occurrence of IP. Genetic testing is helpful for early diagnosis and genetic counseling for families.

Keywords: Chinese; NEMO gene; NF-κB pathway; incontinentia pigmenti; mutation.

Figure 1

Clinical features. (A and B) Brownish linear and whorled hyperpigmentation along Blaschko’s lines on the legs in patient 1. (C and D) Verrucous and linear hyperpigmented lesions and tracing Blaschko’s lines on the trunk and legs in patient 2.

Figure 2

Histological image of patient 1. The net-like keratinized epidermis, epidermal hyperplasia, marked melanin incontinence with many melanophages in the dermis, and infiltration of a few lymphocytes around blood vessels (HE, x200).

Figure 3

NEMO mutation analysis. (A) A normal copy number of the NEMO 4–10 exon in patient 1 according to GAP PCR: lane M: 2000 bp Marker; lane 1: 733 bp in patient 1; lane 2: 733 bp in the positive control; lane 3: 733 bp in the negative control; lane 4: no bands in patient 1; lane 5: 2243 bp, which was expected for exon 4–10 deletion, in the positive control, not in patient 1 (lane 4); lane 6: no bands in the negative control. (B) The sequencing result of patient 1: arrow indicates the position of mutation site, a frameshift mutation, c.723_724insCAGG(p.A242QfsX15) in exon 5 of the NEMO gene. (C) The wild type of patient 1ʹs father. (D) The deletion of exons 4–10 in patient 2 according to NEMO-specific PCR: Marker: DNA ladder 2000–1000-750-500-250 (top to bottom), lane 1 (13,777): 12377-NEMO-E03-10del product (2000 bp). (E) The sequencing result of patient 2: arrow indicates the gap on both sides, the partial sequence of exon 4 of the NEMO gene on the left of the arrow, and the partial downstream sequence of exon 10 of the NEMO gene, confirming the deletion of exons 4–10 of the NEMO gene.