Identification of a recurrent nonsense mutation in HR gene responsible for atrichia with papular lesions in two Kashmiri families. (17th February 2020)

• Record Type: Journal Article
• Authors: Ali, Ghazanfar; Awan, Naheed Bashir; Sadia, ; Khawaja, Abdul Waheed; Foo, Jia Nee; Khor, Chiea Chuen; Chang, Chu‐Hua; Chew, Elaine GuoYan; Kiani, Farhat Rafique; Jelani, Musharraf
• Is Part Of: Journal of gene medicine. Volume 22:Number 5(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-02-17
• Subjects: autosomal recessive -- congenital atrichia -- hair follicle -- HR gene -- Kashmiri families; Genetic transformation -- Periodicals; Gene Transfer -- Periodicals; Gene Therapy -- Periodicals; 616.042
• DOI: 10.1002/jgm.3167
• Languages: English
• ISSNs: 1099-498X

Abstract

Abstract: Background: Congenital atrichia (CA) is a rare form of irreversible alopecia with an autosomal recessive mode of inheritance. This form of hair loss is mainly associated with mutations in the human hairless ( HR ) gene located at chromosome 8p21.3. An additional unique feature atrichia with papular lesions (APL) comprises keratin‐filled cysts known as papules. The present study aimed to uncover the underlying genetic causes of APL in two consanguineous Kashmiri families. Methods: In the present study, two consanguineous families of Kashmiri origin with APL displaying an autosomal recessive mode of inheritance were investigated. Whole exome and Sanger sequencing followed by bioinformatic studies, variant prioritization, Sanger validation and segregation analysis was performed to find the mutation. Results: A recurrent nonsense (NM_005144: c.2818C > T:p.Arg940*) mutation was detected in exon 13 of the human HR gene. Conclusions: Whole exome sequencing analysis has widely been used in the screening of single gene disorders mutations, both in research and diagnostic laboratories. Sanger sequencing alone for genes such as HR becomes expensive and time consuming. Instead, it is recommended that a patient is to screen by whole exome sequencing and then special attention first focuses on known genes of the APL phenotype. This is helpful for intime diagnosis, being more efficient and economic. The results obtained in the present study may contribute to prenatal diagnosis, carrier secreening and the genetic counseling of families with the APL phenotype in Kashmiri poplution.