A KRT6A mutation p.Ile462Asn in a Chinese family with pachyonychia congenita, and identification of maternal mosaicism: a case report
Abstract Background Pachyonychia congenita (PC, OMIM #167200, #167210, #615726, #615728, and #615735) is a rare autosomal dominant disorder caused by keratin gene mutations in KRT6A,KRT6B,KRT6C,KRT16 or KRT17. It is characterized with nail dystrophy and palmoplantar keratoderma (PPK). The most promi...
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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-021-01109-4 |
| _version_ | 1819011110606471168 |
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| author | Yue Li Yumeng Wang Yan Ming Pan Chaolan Zhang Jia Ni Cheng Cao Qiaoyu Ming Li Xu Tianyi |
| author_facet | Yue Li Yumeng Wang Yan Ming Pan Chaolan Zhang Jia Ni Cheng Cao Qiaoyu Ming Li Xu Tianyi |
| author_sort | Yue Li |
| collection | DOAJ |
| description | Abstract Background Pachyonychia congenita (PC, OMIM #167200, #167210, #615726, #615728, and #615735) is a rare autosomal dominant disorder caused by keratin gene mutations in KRT6A,KRT6B,KRT6C,KRT16 or KRT17. It is characterized with nail dystrophy and palmoplantar keratoderma (PPK). The most prominent manifestation is plantar pain. This is a further unusual case of parental mosaicism in PC. Although very rare, germ cell mosaicism should be considered when providing genetic counselling for unaffected parents of a child with PC. Case presentation We report the case of a 5-year-old boy with thickening nails and oral leukokeratosis at birth. He began to develop palmoplantar keratoderma at 2 years old and his sister has similar clinical manifestation characterized with nail discoloration and thickening. A previously reported heterozygous mutation, p.Ile462Asn, was identified in KRT6A in the proband and his affected sister. SNaPshot sequencing revealed mosaicism at a level of 2.5% and 4.7% in DNA from blood and hair bulbs from the unaffected mother. HiSeq deep sequencing demonstrated low-grade mosaicism in the patient’s younger sister and parents. Conclusion These findings indicate the ability of WES and SNaPshot sequencing to detect low-frequency mosaic mutations. Although very rare, germinal mosaicism should be considered when genetic counseling is given to families with presumed spontaneous cases of PC. |
| first_indexed | 2024-12-21T01:22:57Z |
| format | Article |
| id | doaj.art-6128d309cfd3491c90e35bd8d917f942 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-12-21T01:22:57Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-6128d309cfd3491c90e35bd8d917f9422022-12-21T19:20:35ZengBMCBMC Medical Genomics1755-87942021-11-011411710.1186/s12920-021-01109-4A KRT6A mutation p.Ile462Asn in a Chinese family with pachyonychia congenita, and identification of maternal mosaicism: a case reportYue Li0Yumeng Wang1Yan Ming2Pan Chaolan3Zhang Jia4Ni Cheng5Cao Qiaoyu6Ming Li7Xu Tianyi8Departments of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of MedicineDepartments of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of MedicineDepartments of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of MedicineDepartments of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of MedicineDepartments of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of MedicineDepartments of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of MedicineDepartments of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of MedicineDepartments of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of MedicineDepartment of Obstetrics, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract Background Pachyonychia congenita (PC, OMIM #167200, #167210, #615726, #615728, and #615735) is a rare autosomal dominant disorder caused by keratin gene mutations in KRT6A,KRT6B,KRT6C,KRT16 or KRT17. It is characterized with nail dystrophy and palmoplantar keratoderma (PPK). The most prominent manifestation is plantar pain. This is a further unusual case of parental mosaicism in PC. Although very rare, germ cell mosaicism should be considered when providing genetic counselling for unaffected parents of a child with PC. Case presentation We report the case of a 5-year-old boy with thickening nails and oral leukokeratosis at birth. He began to develop palmoplantar keratoderma at 2 years old and his sister has similar clinical manifestation characterized with nail discoloration and thickening. A previously reported heterozygous mutation, p.Ile462Asn, was identified in KRT6A in the proband and his affected sister. SNaPshot sequencing revealed mosaicism at a level of 2.5% and 4.7% in DNA from blood and hair bulbs from the unaffected mother. HiSeq deep sequencing demonstrated low-grade mosaicism in the patient’s younger sister and parents. Conclusion These findings indicate the ability of WES and SNaPshot sequencing to detect low-frequency mosaic mutations. Although very rare, germinal mosaicism should be considered when genetic counseling is given to families with presumed spontaneous cases of PC.https://doi.org/10.1186/s12920-021-01109-4Pachyonychia congentia (PC)Keratin 6AMosaicismWhole exome sequencingSNaPshot sequencingHiSeq deep sequencing |
| spellingShingle | Yue Li Yumeng Wang Yan Ming Pan Chaolan Zhang Jia Ni Cheng Cao Qiaoyu Ming Li Xu Tianyi A KRT6A mutation p.Ile462Asn in a Chinese family with pachyonychia congenita, and identification of maternal mosaicism: a case report BMC Medical Genomics Pachyonychia congentia (PC) Keratin 6A Mosaicism Whole exome sequencing SNaPshot sequencing HiSeq deep sequencing |
| title | A KRT6A mutation p.Ile462Asn in a Chinese family with pachyonychia congenita, and identification of maternal mosaicism: a case report |
| title_full | A KRT6A mutation p.Ile462Asn in a Chinese family with pachyonychia congenita, and identification of maternal mosaicism: a case report |
| title_fullStr | A KRT6A mutation p.Ile462Asn in a Chinese family with pachyonychia congenita, and identification of maternal mosaicism: a case report |
| title_full_unstemmed | A KRT6A mutation p.Ile462Asn in a Chinese family with pachyonychia congenita, and identification of maternal mosaicism: a case report |
| title_short | A KRT6A mutation p.Ile462Asn in a Chinese family with pachyonychia congenita, and identification of maternal mosaicism: a case report |
| title_sort | krt6a mutation p ile462asn in a chinese family with pachyonychia congenita and identification of maternal mosaicism a case report |
| topic | Pachyonychia congentia (PC) Keratin 6A Mosaicism Whole exome sequencing SNaPshot sequencing HiSeq deep sequencing |
| url | https://doi.org/10.1186/s12920-021-01109-4 |
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