Abstract:
Background:
Hair loss has significant psychological and social impacts on individuals affected with
the disease and can cause considerable anxiety among family members. Atrichia with
Papular Lesions (APL; Mendelian Inheritance in Man no. 209500) is an example of
rare genetic hair loss disease that is inherited in an autosomal recessive pattern. It is
characterized by complete irreversible hair loss on the scalp and entire body during
the first months of life with widespread papules (keratin-filled cysts) on the skin that
appear within the first years of life. This disease spreads in consanguineous families
with high fertility rate especially residents in small geographically isolated regions.
Molecular analysis revealed mutations in the hairless gene (HR) on chromosome 8p12
which are considered to be the main cause of this genetic disorder. This gene encodes
a putative transcription factor with a single zinc-finger domain of 1189 amino acids
and is highly expressed in brain and skin. The purpose of our study is to discover the
genetic causes of APL in a number of Palestinian families suffering from this disease.
Methods:
To find the causative mutation for APL, five Palestinian families with the disease
were recruited for our study. Linkage Exclusion Analysis was used at the beginning of
the study to exclude this locus as the cause of the disease. HR gene could not be
excluded in our families thus we performed Sanger Sequencing to identify the
causative mutation in this gene. Sanger sequencing was also used to test the genotype
phenotype segregation within the families and to determine the carrier frequency of
this mutation in 100 healthy controls.
IV
Results:
Sanger sequencing results revealed a single base pair deletion mutation at position
2147 (2147delC), which leads to a frameshift and premature termination codon. This
stop codon is 544 bps downstream in exon 12. This deletion of C causes a frameshift
mutation that changes the reading frame (P716Q fS*186). Also, Sanger sequencing
results showed that this mutation in HR gene segregates perfectly in a recessive mode
of inheritance in all families. This mutation was not detected among 100 healthy
Palestinian controls.
Conclusion:
Our study reports a single base pair deletion in exon 9 of HR gene in a homozygous
form in all affected members of five Palestinian families with Congenital Atrichia.
Mutations in this gene were also discovered to cause APL in people from different
ethnic backgrounds.
Key words:
Atrichia with Papular Lesions (APL), Linkage Exclusion Analysis, Sanger Sequencing, Alopecia, HR gene
