Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis
Abstract Background Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-02-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1076 |
| _version_ | 1827345873721360384 |
|---|---|
| author | Liangshan Li Wenmiao Liu Yinglei Xu Miaomiao Li Qian Tang Bo Yu Renmei Cai Shiguo Liu |
| author_facet | Liangshan Li Wenmiao Liu Yinglei Xu Miaomiao Li Qian Tang Bo Yu Renmei Cai Shiguo Liu |
| author_sort | Liangshan Li |
| collection | DOAJ |
| description | Abstract Background Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to be responsible for ARCI including PNPLA1 which can cause ARCI type 10. The objectives of this study are to describe clinical features of three ARCI patients from two Chinese unrelated families and to identify the underlying causative mutations. Methods Genomic DNA was extracted from peripheral venous blood obtained from the two Chinese ARCI families in Shandong province. Subsequently, targeted regions sequencing (TRS) followed by Sanger sequencing was conducted to identify and validate the likely pathogenic mutations of the ARCI families. Results Genetic analyses revealed four novel PNPLA1 variants that are predicted to be probably to lead to ARCI in three patients of two families. Patient 1 in one family was in compound heterozygous status for c.604delC/p.Arg202Glyfs*27 and c.820dupC/p.Arg274Profs*15, whereas c.738_742delinsCCCACAGATCCTGC/ p.Gly247_Tyr248delinsProGlnIleLeuHis, and c.816dupC/p.Arg274Profs*15 were found in patient 2 and 3 of the other family. In addition, these variants cosegregate in the two pedigrees and are all within highly conserved regions of the PNPLA1 protein, which indicate that the four mutations are likely pathogenic. Conclusion Our findings not only broaden the mutational spectrum of PNPLA1, but also contribute to establishing genotype–phenotype correlations for different forms of ARCI. |
| first_indexed | 2024-03-07T23:19:02Z |
| format | Article |
| id | doaj.art-7c0c744c0ee64222a1203842c2797d73 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:19:02Z |
| publishDate | 2020-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-7c0c744c0ee64222a1203842c2797d732024-02-21T08:58:10ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-02-0182n/an/a10.1002/mgg3.1076Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosisLiangshan Li0Wenmiao Liu1Yinglei Xu2Miaomiao Li3Qian Tang4Bo Yu5Renmei Cai6Shiguo Liu7Medical Genetic Department The Affiliated Hospital of Qingdao University Qingdao ChinaMedical Genetic Department The Affiliated Hospital of Qingdao University Qingdao ChinaMedical Genetic Department The Affiliated Hospital of Qingdao University Qingdao ChinaMedical Genetic Department The Affiliated Hospital of Qingdao University Qingdao ChinaMedical Genetic Department The Affiliated Hospital of Qingdao University Qingdao ChinaDermatological department The Affiliated Hospital of Qingdao University Qingdao ChinaPrenatal Diagnosis Center Qingdao Municipal Hospital Qingdao ChinaMedical Genetic Department The Affiliated Hospital of Qingdao University Qingdao ChinaAbstract Background Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to be responsible for ARCI including PNPLA1 which can cause ARCI type 10. The objectives of this study are to describe clinical features of three ARCI patients from two Chinese unrelated families and to identify the underlying causative mutations. Methods Genomic DNA was extracted from peripheral venous blood obtained from the two Chinese ARCI families in Shandong province. Subsequently, targeted regions sequencing (TRS) followed by Sanger sequencing was conducted to identify and validate the likely pathogenic mutations of the ARCI families. Results Genetic analyses revealed four novel PNPLA1 variants that are predicted to be probably to lead to ARCI in three patients of two families. Patient 1 in one family was in compound heterozygous status for c.604delC/p.Arg202Glyfs*27 and c.820dupC/p.Arg274Profs*15, whereas c.738_742delinsCCCACAGATCCTGC/ p.Gly247_Tyr248delinsProGlnIleLeuHis, and c.816dupC/p.Arg274Profs*15 were found in patient 2 and 3 of the other family. In addition, these variants cosegregate in the two pedigrees and are all within highly conserved regions of the PNPLA1 protein, which indicate that the four mutations are likely pathogenic. Conclusion Our findings not only broaden the mutational spectrum of PNPLA1, but also contribute to establishing genotype–phenotype correlations for different forms of ARCI.https://doi.org/10.1002/mgg3.1076autosomal recessive congenital ichthyosis (ARCI)genetic analysesPNPLA1Sanger sequencingtargeted regions sequencing (TRS) |
| spellingShingle | Liangshan Li Wenmiao Liu Yinglei Xu Miaomiao Li Qian Tang Bo Yu Renmei Cai Shiguo Liu Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis Molecular Genetics & Genomic Medicine autosomal recessive congenital ichthyosis (ARCI) genetic analyses PNPLA1 Sanger sequencing targeted regions sequencing (TRS) |
| title | Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis |
| title_full | Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis |
| title_fullStr | Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis |
| title_full_unstemmed | Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis |
| title_short | Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis |
| title_sort | targeted regions sequencing identified four novel pnpla1 mutations in two chinese families with autosomal recessive congenital ichthyosis |
| topic | autosomal recessive congenital ichthyosis (ARCI) genetic analyses PNPLA1 Sanger sequencing targeted regions sequencing (TRS) |
| url | https://doi.org/10.1002/mgg3.1076 |
| work_keys_str_mv | AT liangshanli targetedregionssequencingidentifiedfournovelpnpla1mutationsintwochinesefamilieswithautosomalrecessivecongenitalichthyosis AT wenmiaoliu targetedregionssequencingidentifiedfournovelpnpla1mutationsintwochinesefamilieswithautosomalrecessivecongenitalichthyosis AT yingleixu targetedregionssequencingidentifiedfournovelpnpla1mutationsintwochinesefamilieswithautosomalrecessivecongenitalichthyosis AT miaomiaoli targetedregionssequencingidentifiedfournovelpnpla1mutationsintwochinesefamilieswithautosomalrecessivecongenitalichthyosis AT qiantang targetedregionssequencingidentifiedfournovelpnpla1mutationsintwochinesefamilieswithautosomalrecessivecongenitalichthyosis AT boyu targetedregionssequencingidentifiedfournovelpnpla1mutationsintwochinesefamilieswithautosomalrecessivecongenitalichthyosis AT renmeicai targetedregionssequencingidentifiedfournovelpnpla1mutationsintwochinesefamilieswithautosomalrecessivecongenitalichthyosis AT shiguoliu targetedregionssequencingidentifiedfournovelpnpla1mutationsintwochinesefamilieswithautosomalrecessivecongenitalichthyosis |