Analysis of IKBKG/NEMO gene in five Japanese cases of incontinentia pigmenti with retinopathy: fine genomic assay of a rare male case with mosaicism.
Journal
Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
28
05
2020
accepted:
26
08
2020
revised:
25
08
2020
pubmed:
11
9
2020
medline:
29
6
2021
entrez:
10
9
2020
Statut:
ppublish
Résumé
Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis that is usually lethal in utero in males, though exceptionally they survive very rarely either with Klinefelter syndrome or a somatic mosaicism. We performed genomic analysis of five Japanese IP patients including a rare boy case, all of whom were definite cases with retinopathy. Four patients including the boy revealed the recurrent exon 4-10 deletion in the sole known causative gene IKBKG/NEMO, which was confirmed by various specific PCR techniques. The boy's saliva DNA showed a mosaicism consisting of the deletion and intact alleles, but his blood DNA did not. Relative quantification analysis of the real-time PCR data by ∆∆CT method estimated the mosaicism ratio of the boy's saliva as 45:55 (deletion:intact). A genomic analysis for the recurrent deletion at the nucleotide sequence level has been performed directly using patient's DNA and it has been clarified that the breakpoints are within two MER67B repeats in the intron 3 and downstream of exon 10. This is the first report of the assay for the mosaicism ratio of a male IP case with a recurrent exon 4-10 deletion of IKBKG/NEMO and the sequencing analysis of the breakpoints of the recurrent deletion directly using patient's sample.
Identifiants
pubmed: 32908217
doi: 10.1038/s10038-020-00836-3
pii: 10.1038/s10038-020-00836-3
doi:
Substances chimiques
IKBKG protein, human
0
I-kappa B Kinase
EC 2.7.11.10
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
205-214Subventions
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP18ek0109301
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : JP17K11447
Commentaires et corrections
Type : ErratumIn
Références
Landy SJ, Donnai D. Incontinentia pigmenti (Bloch-Sulzberger syndrome). J Med Genet. 1993;30:53–9.
doi: 10.1136/jmg.30.1.53
Smahi A, Courtois G, Vabres P, Yamaoka S, Heuertz S, Munnich A, et al. Genomic rearrangement in NEMO impairs NF-κB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature. 2000;405:466–72.
doi: 10.1038/35013114
Parrish JE, Scheuerle AE, Lewis RA, Levy ML, Nelson DL. Selection against mutant alleles in blood leukocytes is a consistent feature in Incontinentia Pigmenti type 2. Hum Mol Genet. 1996;5:1777–83.
doi: 10.1093/hmg/5.11.1777
Woffendin H, Jakins T, Jouet M, Stewart H, Landy S, Haan E, et al. X-inactivation and marker studies in three families with incontinentia pigmenti: implications for counselling and gene localisation. Clin Genet. 1999;55:55–60.
doi: 10.1034/j.1399-0004.1999.550110.x
Kunze J, Frenzel UH, Hüttig E, Grosse F-R, Wiedemann H-R. Klinefelter’s syndrome and incontinentia pigmenti Bloch-Sulzberger. Hum Genet. 1977;35:237–40.
doi: 10.1007/BF00393976
Hull S, Arno G, Thomson P, Mutch S, Webster AR, Rai H, et al. Somatic mosaicism of a novel IKBKG mutation in a male patient with incontinentia pigmenti. Am J Med Genet A. 2015;167:1601–4.
doi: 10.1002/ajmg.a.37004
Fusco F, Conte MI, Diociaiuti A, Bigoni S, Branda MF, Ferlini A, et al. Unusual father-to-daughter transmission of incontinentia pigmenti due to mosaicism in IP males. Pediatrics. 2017;140:e20162950.
doi: 10.1542/peds.2016-2950
Carney RG. Incontinentia pigmenti—a world statistical analysis. Arch Dermatol. 1976;112:535–42.
doi: 10.1001/archderm.1976.01630280059017
Goldberg MF, Custis PH. Retinal and other manifestations of incontinentia pigmenti (Bloch-Sulzberger syndrome). Ophthalmology. 1993;100:1645–54.
doi: 10.1016/S0161-6420(93)31422-3
Fusco F, Pescatore A, Steffann J, Bonnefont JP, De Oliveira J, Lioi MB, et al. Clinical utility gene card: for incontinentia pigmenti. Eur J Hum Genet. 2019;27:1894–900.
doi: 10.1038/s41431-019-0463-9
Fusco F, Mercadante V, Miano MG, Ursini MV. Multiple regulatory regions and tissue-specific transcription initiation mediate the expression of NEMO/IKKγ gene. Gene. 2006;383:99–107.
doi: 10.1016/j.gene.2006.07.022
Aradhya S, Bardaro T, Galgóczy P, Yamagata T, Esposito T, Patlan H, et al. Multiple pathogenic and benign genomic rearrangements occur at a 35 kb duplication involving the NEMO and LAGE2 genes. Hum Mol Genet. 2001;10:2557–67.
doi: 10.1093/hmg/10.22.2557
Bardaro T, Falco G, Sparago A, Mercadante V, Gean Molins E, Tarantino E, et al. Two cases of misinterpretation of molecular results in incontinentia pigmenti, and a PCR-based method to discriminate NEMO/IKKγ gene deletion. Hum Mutat. 2003;21:8–11.
doi: 10.1002/humu.10150
Aradhya S, Woffendin H, Jakins T, Bardaro T, Esposito T, Smahi A, et al. A recurrent deletion in the ubiquitously expressed NEMO (IKK-γ) gene accounts for the vast majority of incontinentia pigmenti mutations. Hum Mol Genet. 2001;10:2171–9.
doi: 10.1093/hmg/10.19.2171
Döffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A, et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-κB signaling. Nat Genet. 2001;27:277–85.
doi: 10.1038/85837
Garrod AE. Peculiar pigmentation of the skin in an infant. Trans Clin Soc Lond. 1906;39:216.
Berlin AL, Paller AS, Chan LS. Incontinentia pigmenti: a review and update on the molecular basis of pathophysiology. J Am Acad Dermatol. 2002;47:169–87.
doi: 10.1067/mjd.2002.125949
Okita M, Nakanishi G, Fujimoto N, Shiomi M, Yamada T, Wataya-Kaneda M, et al. NEMO gene rearrangement (exon 4–10 deletion) and genotype-phenotype relationship in Japanese patients with incontinentia pigmenti and review of published work in Japanese patients. J Dermatol. 2013;40:272–6.
doi: 10.1111/1346-8138.12091
Nakao S, Nishina S, Tanaka S, Yoshida T, Yokoi T, Azuma N. Early laser photocoagulation for extensive retinal avascularity in infants with incontinentia pigmenti. Jpn J Ophthalmol. 2020. https://doi.org/10.1007/s10384-020-00768-7 . In press.
Steffann J, Raclin V, Smahi A, Woffendin H, Munnich A, Kenwrick SJ, et al. A novel PCR approach for prenatal detection of the common NEMO rearrangement in incontinentia pigmenti. Prenat Diagn. 2004;24:384–8.
doi: 10.1002/pd.889
Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol. 2000;132:365–86.
pubmed: 10547847
Untergasser A, Nijveen H, Rao X, Bisseling T, Geurts R, Leunissen JA. Primer3Plus, an enhanced web interface to Primer3. Nucleic Acids Res. 2007;35:W71–4.
doi: 10.1093/nar/gkm306
Zou CC, Zhao ZY. Clinical and molecular analysis of NF-κB essential modulator in Chinese incontinentia pigmenti patients. Int J Dermatol. 2007;46:1017–22.
doi: 10.1111/j.1365-4632.2007.03365.x
Sakowicz A, Pietrucha T, Rybak-Krzyszkowska M, Huras H, Gach A, Sakowicz B, et al. Double hit of NEMO gene in preeclampsia. PLoS ONE. 2017;12:e0180065.
doi: 10.1371/journal.pone.0180065
Riahi A, Chabouni-Bouhamed H, Kharrat M. Prevalence of BRCA1 and BRCA2 large genomic rearrangements in Tunisian high risk breast/ovarian cancer families: Implications for genetic testing. Cancer Genet. 2017;210:22–7.
doi: 10.1016/j.cancergen.2016.11.002
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2
doi: 10.1006/meth.2001.1262