A Novel <i>CDH1</i> Variant Identified in a Chinese Family with Blepharocheilodontic Syndrome
The goal of the current study was to identify the pathogenic gene variant in a Chinese family with Blepharocheilodontic (BCD) syndrome. Whole-exome sequencing (WES) and Sanger sequencing were used to identify the pathogenic gene variant. The harmfulness of the variant was predicted by bioinformatics...
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MDPI AG
2022-11-01
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| Series: | Diagnostics |
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| author | Bichen Lin Yang Liu Lanxin Su Hangbo Liu Hailan Feng Miao Yu Haochen Liu |
| author_facet | Bichen Lin Yang Liu Lanxin Su Hangbo Liu Hailan Feng Miao Yu Haochen Liu |
| author_sort | Bichen Lin |
| collection | DOAJ |
| description | The goal of the current study was to identify the pathogenic gene variant in a Chinese family with Blepharocheilodontic (BCD) syndrome. Whole-exome sequencing (WES) and Sanger sequencing were used to identify the pathogenic gene variant. The harmfulness of the variant was predicted by bioinformatics. We identified a novel heterozygous missense variant c.1198G>A (p.Asp400Asn) in the <i>CDH1</i> gene in the proband and his mother with BCD syndrome. The sequencing results of three healthy individuals in this family are wild type. This result is consistent with familial co-segregation. According to ReVe, REVEL, CADD, gnomAD, dbSNP, and the classification of pathogenic variants with the standards of the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG), c.1198G>A (p.Asp400Asn) is predicted to be a likely pathogenic. We observed that variant c.1198G>A (p.Asp400Asn) was located in the extracellular cadherin-type repeats in CDH1. Amino acid sequence alignment of the CDH1 protein among multiple species showed that Asp400 was highly evolutionarily conserved. The conformational analysis showed that this variant might cause structural damage to the CDH1 protein. Phenotypic analysis revealed unique dental phenotypes in patients with BCD syndrome, such as oligodontia, conical-shaped teeth, and notching of the incisal edges. Our results broaden the variation spectrum of BCD syndrome and phenotype spectrum of CDH1, which can help with the clinical diagnosis, treatment, and genetic counseling in relation to BCD syndrome. |
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| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-09T17:08:18Z |
| publishDate | 2022-11-01 |
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| series | Diagnostics |
| spelling | doaj.art-5e979b39fd8d49d8b7f8025dd14f16d82023-11-24T14:15:49ZengMDPI AGDiagnostics2075-44182022-11-011212293610.3390/diagnostics12122936A Novel <i>CDH1</i> Variant Identified in a Chinese Family with Blepharocheilodontic SyndromeBichen Lin0Yang Liu1Lanxin Su2Hangbo Liu3Hailan Feng4Miao Yu5Haochen Liu6First Clinical Division, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaThe goal of the current study was to identify the pathogenic gene variant in a Chinese family with Blepharocheilodontic (BCD) syndrome. Whole-exome sequencing (WES) and Sanger sequencing were used to identify the pathogenic gene variant. The harmfulness of the variant was predicted by bioinformatics. We identified a novel heterozygous missense variant c.1198G>A (p.Asp400Asn) in the <i>CDH1</i> gene in the proband and his mother with BCD syndrome. The sequencing results of three healthy individuals in this family are wild type. This result is consistent with familial co-segregation. According to ReVe, REVEL, CADD, gnomAD, dbSNP, and the classification of pathogenic variants with the standards of the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG), c.1198G>A (p.Asp400Asn) is predicted to be a likely pathogenic. We observed that variant c.1198G>A (p.Asp400Asn) was located in the extracellular cadherin-type repeats in CDH1. Amino acid sequence alignment of the CDH1 protein among multiple species showed that Asp400 was highly evolutionarily conserved. The conformational analysis showed that this variant might cause structural damage to the CDH1 protein. Phenotypic analysis revealed unique dental phenotypes in patients with BCD syndrome, such as oligodontia, conical-shaped teeth, and notching of the incisal edges. Our results broaden the variation spectrum of BCD syndrome and phenotype spectrum of CDH1, which can help with the clinical diagnosis, treatment, and genetic counseling in relation to BCD syndrome.https://www.mdpi.com/2075-4418/12/12/2936<i>CDH1</i>Blepharocheilodontic syndromegene varianttooth agenesis |
| spellingShingle | Bichen Lin Yang Liu Lanxin Su Hangbo Liu Hailan Feng Miao Yu Haochen Liu A Novel <i>CDH1</i> Variant Identified in a Chinese Family with Blepharocheilodontic Syndrome Diagnostics <i>CDH1</i> Blepharocheilodontic syndrome gene variant tooth agenesis |
| title | A Novel <i>CDH1</i> Variant Identified in a Chinese Family with Blepharocheilodontic Syndrome |
| title_full | A Novel <i>CDH1</i> Variant Identified in a Chinese Family with Blepharocheilodontic Syndrome |
| title_fullStr | A Novel <i>CDH1</i> Variant Identified in a Chinese Family with Blepharocheilodontic Syndrome |
| title_full_unstemmed | A Novel <i>CDH1</i> Variant Identified in a Chinese Family with Blepharocheilodontic Syndrome |
| title_short | A Novel <i>CDH1</i> Variant Identified in a Chinese Family with Blepharocheilodontic Syndrome |
| title_sort | novel i cdh1 i variant identified in a chinese family with blepharocheilodontic syndrome |
| topic | <i>CDH1</i> Blepharocheilodontic syndrome gene variant tooth agenesis |
| url | https://www.mdpi.com/2075-4418/12/12/2936 |
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