Identification of a recurrent nonsense mutation in HR gene responsible for atrichia with papular lesions in two Kashmiri families.
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.
['Ali|Ghazanfar|G|0000-0002-6172-9503', 'Awan|Naheed Bashir|NB|', 'Sadia|||', 'Khawaja|Abdul Waheed|AW|', 'Foo|Jia Nee|JN|', 'Khor|Chiea Chuen|CC|', 'Chang|Chu-Hua|CH|', 'Chew|Elaine GuoYan|EG|', 'Kiani|Farhat Rafique|FR|', 'Jelani|Musharraf|M|0000-0002-3421-0079']
D000483:Alleles D000505:Alopecia D018389:Codon, Nonsense D005091:Exons D005190:Family D005260:Female D018859:Hair Follicle D006801:Humans D008297:Male D009154:Mutation D010154:Pakistan D010375:Pedigree D010641:Phenotype D012872:Skin Diseases, Vesiculobullous D014157:Transcription Factors D000073359:Whole Exome Sequencing
HR gene Kashmiri families congenital atrichia autosomal recessive hair follicle