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. 2014 Sep 12;9(9):e106656.
doi: 10.1371/journal.pone.0106656. eCollection 2014.

Two novel tyrosinase (TYR) gene mutations with pathogenic impact on oculocutaneous albinism type 1 (OCA1)

Vadieh Ghodsinejad Kalahroudi  1 , Behnam Kamalidehghan  2 , Ahoura Arasteh Kani  3 , Omid Aryani  3 , Mahdi Tondar  4 , Fatemeh Ahmadipour  2 , Lip Yong Chung  2 , Massoud Houshmand  5
Affiliations

Two novel tyrosinase (TYR) gene mutations with pathogenic impact on oculocutaneous albinism type 1 (OCA1)

Vadieh Ghodsinejad Kalahroudi et al. PLoS One. .

Abstract

Oculocutaneous albinism (OCA) is a heterogeneous group of autosomal recessive disorders resulting from mutations of the tyrosinase (TYR) gene and presents with either complete or partial absence of pigment in the skin, hair and eyes due to a defect in an enzyme involved in the production of melanin. In this study, mutations in the TYR gene of 30 unrelated Iranian OCA1 patients and 100 healthy individuals were examined using PCR-sequencing. Additionally, in order to predict the possible effects of new mutations on the structure and function of tyrosinase, these mutations were analyzed by SIFT, PolyPhen and I-Mutant 2 software. Here, two new pathogenic p.C89S and p.H180R mutations were detected in two OCA1 patients. Moreover, the R402Q and S192Y variants, which are common non-pathogenic polymorphisms, were detected in 17.5% and 35% of the patients, respectively. The outcome of this study has extended the genotypic spectrum of OCA1 patients, which paves the way for more efficient carrier detection and genetic counseling.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Agarose gel electrophoresis of PCR product.
The PCR products electrophoresed on a 1.5% agarose gel. From left: lane 1: exon 1–1 (700 bp), lane 2: exon 1–2 (500 bp), lane 3: exon 1–3 (600 bp), lane 4: exon 1–4 (500 bp), Lane 5: DNA ladder (Thermo Scientific Gene Ruler 100 bp #SM0241/2/3), Lane 6: Exon 2 (450 bp), Lane 7: Exon 3 (300 bp), Lane 8 Exon 4(790 bp), Lane 9: Exon5 (920 bp).
Figure 2
Figure 2. Reported mutations in this study are distributed on the TYR gene.
Figure 3
Figure 3. Distribution of mutations on the TYR gene in OCA1 patients.
Bar diagram indicates the percentage of mutations that were found in this study.
Figure 4
Figure 4. DNA sequencing result from Exon 1 of the TYR gene, showing c.265 T>A mutation.
A: Normal Sequence from control. B: Sequence from unaffected parents showing the c.265 T>A heterozygous mutation. C: Sequence from patient 1 with a new c.265 T>A homozygous mutation.
Figure 5
Figure 5. DNA sequencing result from Exon 1 of the TYR gene showing c.539 A>G mutation.
A: Normal Sequence from control and unaffected father. B: Sequence from patient 19 and an unaffected mother showing the c.539 A>G heterozygous mutation.
Figure 6
Figure 6. Database of tyrosinase (TYR) gene mutations.
The mutations identified in OCA1 for each exon are described in the upper and lower half of the schema.
See this image and copyright information in PMC

References

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