A novel pathogenic mutation in the NEMO gene in a family with incontinentia pigmenti / 中华皮肤科杂志

Objective:To identify gene mutations in a family with incontinentia pigmenti, in order to confirm pathogenic mutations.Methods:Clinical data were collected from all patients in a family with incontinentia pigmenti. DNA was extracted from peripheral blood samples obtained from the patients, healthy members in the family, and 100 unrelated healthy controls, and Sanger sequencing was performed for all exons and their flanking sequences of the NEMO gene.Results:Totally, there were 4 patients in the 4-generation family, who all presented with typical skin lesions and different symptoms. Genetic testing indicated that the proband and the other 3 patients all carried a heterozygous nonsense mutation c.1153C>T (p.Gln385X) at position 1153 in exon 8 of the NEMO gene, which led to the substitution of the glutamine codon (CAG) by the termination codon (TAG) at amino acid position 385. The mutation was not identified in the 14 healthy relatives or 100 unrelated healthy controls. The mutation cosegregated with incontinentia pigmenti in the family. Database searching confirmed the mutation to be a novel nonsense mutation, and it was considered as a very strong pathogenic locus according to the American College of Medical Genetic and Genomics guidelines.Conclusion:The mutation c.1153C>T in the NEMO gene is associated with the occurrence of incontinentia pigmenti in this family.

Mosaic mutation in the NEMO gene causes incontinentia pigmenti in a male patient / 中华皮肤科杂志

Objective To identify mutations in the NEMO gene in a family with incontinentia pigmenti.Methods Clinical data were collected from the proband,and peripheral blood samples were obtained from the proband,her parents and 200 healthy controls.Multiplex PCR was performed to detect heterozygous deletion of exons 4-10 of the NEMO gene in the blood samples of the proband and her parents.Then,PCR was performed to amplify exons 2,3-10 of the NEMO gene in all the blood samples,and all exons in the gene coding region and their flanking sequences were subjected to DNA sequencing.DNA was extracted from paraffin-embedded lesional tissue of the proband's father,and PCR was performed to amplify exon 10 of the NEMO gene and its flanking sequence followed by DNA sequencing.Results The deletion of exons 4-10 of the NEMO gene was undetected in the peripheral blood of the proband or her father.Sanger sequencing showed that there was a heterozygous mutation c.1236dupA in exon 10 of the NEMO gene in the peripheral blood of the proband,which led to a mutation in amino acid residues (p.H413fs*7).The c.1236dupA mutation was not found in the peripheral blood of the proband's parents,while a mosaic mutation c.1236dupA was detected in the DNA from lesional tissues of the proband's father.Conclusion The mutation c.1236dupA in the NEMO gene may be the underlying cause of incontinentia pigmenti in the proband and her father.

A Case of Incontinentia Pigmenti with Multiple Brain Infarction

Incontinentia pigmenti (IP) is a rare X-linked dominant disease that is typically lethal to males and usually affect female patients. IP is a neurocutaneous disorder, involving the ectodermal tissues such as the skin, eyes, teeth, hair, and central nervous system. The pathogenesis of IP is linked to the gene mutation in the NF-kappa B essential modulator (NEMO) on chromosome Xq28. We experienced one case of newborn with multiple vesiculobullous skin lesions over the entire body after birth. Skin biopsy and histologic studies revealed suspected IP stage I and the genetic analysis of the NEMO confirmed IP diagnosis. A brain MRI showed multiple cerebral infarctions and the infant has shown delayed development in follow-up clinic.

Utility of molecular studies in incontinentia pigmenti patients.

The diagnosis of incontinentia pigmenti (IP) is fairly easy in the presence of classical features, but can be difficult in cases with partial or non-classical features, especially in the parents. The demonstration that the disease is caused by mutations in the NEMO gene, has remarkably improved genetic counselling for this disorder. We present four families of IP in whom molecular studies established an unequivocal diagnosis in the affected daughters, and showed two mothers to be carriers, thus allowing accurate genetic counselling and prenatal diagnosis.

A Genetic Study in a Patient with Incontinentia Pigmenti / 대한피부과학회지

Incontinentia pigmenti (IP) is a rare X-linked dominant, multisystem genodermatosis that affects ectoderm-derived structures. Its cutaneous manifestations are usually subdivided into the vesicular, verrucous, hyperpigmented, and hypopigmented or atrophic stages. IP can also affect other ectoderm-derived structures, such as, hair, nails, teeth, eyes, and the central nervous and musculoskeletal systems. About 80% of IP patients have genomic deletions of exons 4~10 of the NEMO (NF-kappaB-Essential MOdulator) gene, also known as the IKKgamma (gamma-subunit of the inhibitor kappaB kinase), which is essential for the activation of the NF-kappaB pathway. The female infant presented in this case report was born to healthy non-consanguineous parents and showed vesiculopustular eruptions with a NEMO gene rearrangement. No IP case has been previously reported to be related to a NEMO gene mutation in South Korea. In other words, this is the first report to confirm the relation between IP and mutation of the NEMO gene in Koreans.