G Model
DESC-2739; No. of Pages 3 Journal of Dermatological Science xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Dermatological Science journal homepage: www.jdsjournal.com
Letter to the Editor Oculocutaneous albinism (OCA) in Colombia: First molecular screening of the TYR and OCA2 genes in South America
Keywords: Oculocutaneous albinism; TYR gene; OCA2 gene; Colombia; South America
Oculocutaneous albinism (OCA) is a group of autosomal recessive disorders of the melanin biosynthesis pathway, characterized by complete lack or generalized reduction in pigmentation of hair, skin and eyes [1]. Individuals affected by OCA are at high risk of ultraviolet (UV) radiation-induced skin cancer due to the lack of photoprotective melanin. In addition, reduced visual acuity is observed mainly because early melanin precursors are vital for normal visual development in mammalian embryogenesis [2]. Genetically, seven nonsyndromic types of OCA have been described, OCA1-OCA 7 [3]. OCA1A (MIM #203100), the most common and severe form known is caused by mutations in TYR (MIM *606933) gene whereas OCA2 (MIM #203200), is a milder phenotype and the second most common type of OCA caused by mutations in OCA2 (MIM *611409) gene [4]. It is estimated that 80% of worldwide cases of OCA are explained by mutations in these two genes, TYR and OCA2, accounting for 50% and 30% cases respectively [5]. Here, we report four novel mutations and five mutations previously reported in the albinism databases, in a Colombian cohort. We analyzed 36 individuals with OCA belonging to 23 independent families from different Colombian regions. Individuals were referred by the Albino Organization ‘‘Fundacio´n Contraste – Albinos por Colombia’’. Written informed consent/assent was obtained from all participants or legal guardians. All individuals analyzed had different degrees of hypopigmentation on skin, hair and eyes, plus typical ocular landmarks of the condition representing the clinical spectrum of OCA phenotypes. Hematologic abnormalities, bleeding diathesis or deafness were absent in all individuals discarding possible syndromes such as HermanskyPudlak among others. Genomic DNA was isolated from blood sample using the kit DNA 20001 (Corpogen, Colombia). Initially, the 23 unrelated cases were screened for mutations in the coding region of TYR gene by Sanger sequencing using Macrogen service (Seoul, Republic of Korea). If either one or no mutations were found in TYR, we proceeded to sequence the coding region of OCA2 using the same platform. Mutational screening of TYR and OCA2 genes revealed 9 mutations (Table 1). Of these, 5 have been reported in the albinism databases as follows: p.D42N (rs200960909), p.G47D (rs61753180),
and p.R77Q (rs61753185) found in TYR and p.R53GfsX49 and p.A787T (rs142988897) in OCA2. Additionally, 4 novel mutations in TYR were found: two missense mutations referred as p.C55G (rs367543067) and p.C247R (rs367543068), and two nonsense mutations referred as p.S184X (rs367543066) and p.I209SfsX32. These mutations were not detected in 100 unaffected chromosomes indicating that they are likely pathogenic mutations rather than ethnic-specific polymorphisms. Family pedigrees of 3 novel mutations are shown in Fig. 1. The novel nonsense mutations S184X and I209SfsX32, both cause a stop codon in exon 1, thereby truncating tyrosinase enzyme activity. Bioinformatic analysis on the novel missense C55G and C247R mutations using SIFT and PolyPhen2 servers (December 2013), predict an impact in structure and function of the protein (SIFT score: 0; PP2 score: 1 for both mutations). Cysteine, apart from forming disulfide bridges to stabilize the native structure of the proteins is also part of the tyrosinase catalytic domain. To highlight, 11/11 individuals with homozygous or compound heterozygous mutations in TYR, have no discernible pigmentation in hair, skin and eyes (Table 1). The G47D was initially found in a small sample of 5 individuals from our population [6], here the mutation was found to be the most frequent within our study sample with 5 homozygous and 4 compound heterozygous cases. The remaining 12 individuals presented an albinism phenotype with variable degree of hypopigmentation (coloring ranges from yellow to light brown hair and from blue to brownish irides). Furthermore, when we analyzed individuals from ‘‘El Santuario and Marinilla, Antioquia’’, genetically isolated northwestern towns in Colombia well known for its high albinism prevalence [7], all were homozygous for the previously reported p.A787T mutation in OCA2 gene (OCA_24 represents all individuals from the region). Interestingly, the case OCA_14 who is native from ‘‘Samana´, Caldas’’ at 252 km on road from El Santuario, is also homozygous for the p.A787T mutation. He did not inform any family relationship to El Santuario or Marinilla, though the towns are geographically close. In 7/12 cases with variable hypopigmentation, no mutations were found in the TYR or OCA2 genes. Of these, cases OCA_8, 10, 11 and 17 were heterozygous for the frequent polymorphism p.R402Q (rs1126809) in the TYR gene. Additionally, case OCA_17 was homozygous for the polymorphism p.R305W (rs1800401) in the OCA2 gene. Also, individual OCA_22 who has one novel TYR mutation, also has the p.R305W polymorphism, whereas individual OCA_07 who also has one novel mutation in TYR presents both the p.R402Q and the p.R305W polymorphisms. These two polymorphisms (R402Q and R305W) by themselves have been reported as not sufficient to cause albinism, since unaffected individuals have been found to be homozygous for these polymorphisms [8]. In particular, the polymorphism R402Q
http://dx.doi.org/10.1016/j.jdermsci.2014.09.011 0923-1811/ß 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Urtatiz O, et al. Oculocutaneous albinism (OCA) in Colombia: First molecular screening of the TYR and OCA2 genes in South America. J Dermatol Sci (2014), http://dx.doi.org/10.1016/j.jdermsci.2014.09.011
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DESC-2739; No. of Pages 3 Letter to the Editor / Journal of Dermatological Science xxx (2014) xxx–xxx
2
Table 1 Mutational analysis in the TYR and OCA2 genes in 23 cases with OCA.
Individual code Phenotype Age Sex TYR gene
OCA2 gene
Variant 1 Nucleotide change
Aminoacid change
Variant 2 Nucleotide change
Aminoacid change
Variant 1 Nucleotide change
Aminoacid change
Variant 2 Nucleotide change
c.913C>T
p.R305W*
N.F
c.913C>T
p.R305W*
OCA_01
NP
27
F
c.140G>A
p.G47D
c.140G>A
p.G47D
–
OCA_13
NP
35
M
c.140G>A
p.G47D
c.140G>A
p.G47D
–
OCA_16
NP
52
M
c.140G>A
p.G47D
c.140G>A
p.G47D
–
OCA_19
NP
25
M
c.140G>A
p.G47D
c.140G>A
p.G47D
–
OCA_20
NP
42
F
c.140G>A
p.G47D
c.140G>A
p.G47D
–
OCA_02
NP
5
F
c.140G>A
p.G47D
c.124G>A
p.D42N
–
OCA_06
NP
30
M
c.140G>A
p.G47D
c.124G>A
p.D42N
–
OCA_21
NP
62
M
c.551C>G
p.S184X
c.140G>A
p.G47D
–
OCA_18
NP
1
F
c.580delA
p.I209SfsX32 c.140G>A
p.G47D
–
OCA_05
NP
19
F
c.163 T>G
p.C55G
c.124G>A
p.D42N
–
p.R77Q
–
Aminoacid change
OCA_12
NP
35
M
c.230G>A
p.R77Q
c.230G>A
OCA_22
VP
16
M
c.551C>G
p.S184X
N.F
OCA_07
VP
52
M
c.739T>C
p.C247R
c.1205G>A
OCA_14
VP
23
M
N.F
C.2359G>A p.A787T
C.2359G>A p.A787T C.2359G>A p.A787T
p.R402Q*
OCA_24
VP
60
M
N.F
C.2359G>A p.A787T
OCA_04
VP
21
M
N.F
c.157delA
OCA_08
VP
29
F
c.1205G>A p.R402Q*
N.F
OCA_10
VP
18
M
c.1205G>A p.R402Q*
N.F
N.F
OCA_11
VP
31
F
c.1205G>A p.R402Q*
N.F
N.F
OCA_17
VP
56
M
c.1205G>A p.R402Q*
N.F
OCA_03
VP
38
M
N.F
N.F
OCA_09
VP
27
M
N.F
N.F
OCA_15
VP
22
F
N.F
N.F
N.F
p.R53GfsX49 N.F
N.F
c.913C>T
p.R305W*
c.913C>T
p.R305W*
Novel variants are shaded gray. The OCA2 gene was not characterized in individuals with two mutations in TYR. Pathogenic polymorphisms have an asterisk. NP: no pigmentation in hair, skin and eyes; VP: variable pigmentation in hair, skin and ayes; NF: not found.
OCA_05
OCA_18
A I209SfsX32
D42N
G47D
I209SfsX32 / G47D
C55G
D42N / C55G
D42N
OCA_22
B S184X
S184X / S184X R305W
R305W
S184X / R305W
in TYR produces a thermolabile tyrosinase where at physiological temperature (37 8C) has reduced activity and is retained in the endoplasmic reticulum of melanocytes [9]. The R305W polymorphism in OCA2 has been proposed to interact with MC1R gene to explain light skin completion and visual dysfunction in Caucasian population [10]. Thus, it has been proposed that essential modifiers could explain a partial albinism phenotype [4], however until we find the genes causing albinism in these individuals it is difficult to predict how these variants may be contributing to the phenotype. In conclusion, even though our cohort is small, we have identified two novel nonsense mutations and two novel missense mutations. Individuals having two affected alleles in TYR had no discernible pigmentation in hair, skin and eyes, whereas individuals with a single affected allele showed variable degrees of hypopigmentation (Fig. 1B). We can appreciate that G47D and A787T mutations are common in Central and Northwestern regions of Colombia, respectively. Our results provide the first insights of the molecular basis of albinism in Colombia and in South America, however large-cohort studies are still needed to have a record of Colombian albinism mutations and its respective frequencies. Acknowledgements
Fig. 1. Family pedigrees of cases OCA_18, 0CA_05 and OCA_22. Arrow indicates the proband. Proband from OCA_18 inherited a novel TYR I209SfsX32 mutation from her father whereas proband from OCA_05 inherited a novel TYR C55G mutation from her mother; both cases are compound heterozygous (A, top). Proband from OCA_22 inherited the novel S184X mutation in TYR from his father and the polymorphism R305W in OCA2 from his mother. The proband and his older sister have the same variable hypopigmentation phenotype and ocular anomalies typical of OCA, however the affected sister does not have the polymorphism. Non-affected sibling also has the S184X mutation and the R305W polymorphism suggesting the presence of a second mutation in one of the other known genes or a yet unidentified gene (B, bottom).
We want to thank each one of the individuals and families who participated in this study. Special thanks to the Fundacio´n Contraste – Albinos por Colombia and to the Hospitals ‘‘San Juan de Dios’’ of Marinilla and Santuario towns. This work was supported by the Vicedecanatura de Investigaciones y Posgrados 2013, Universidad de los Andes, given to Maria Claudia Lattig and to Oscar Urtatiz.
Please cite this article in press as: Urtatiz O, et al. Oculocutaneous albinism (OCA) in Colombia: First molecular screening of the TYR and OCA2 genes in South America. J Dermatol Sci (2014), http://dx.doi.org/10.1016/j.jdermsci.2014.09.011
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DESC-2739; No. of Pages 3 Letter to the Editor / Journal of Dermatological Science xxx (2014) xxx–xxx
References [1] Gronskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis 2007;2:43. [2] Lavado A, Jeffery G, Tovar V, de la Villa P, Montoliu L. Ectopic expression of tyrosine hydroxylase in the pigmented epithelium rescues the retinal abnormalities and visual function common in albinos in the absence of melanin. J Neurochem 2006;96:1201–11. [3] Montoliu L, Grønskov K, Wei AH, Martı´nez-Garcı´a M, Ferna´ndez A, Arveiler B, et al. Increasing the complexity: new genes and new types of albinism. Pigment Cell Melanoma Res 2013;27:11–8. [4] Simeonov DR, Wang X, Wang C, Sergeev Y, Dolinska M, Bower M, et al. DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics. Hum Mutat 2013;34:827–35. [5] Roorick C, Morice-Picard F, Lasseaux E, Cailley D, Dollfus H, et al. High resolution mapping of OCA2 intragenic rearrangements and identification of a founder effect associated with a deletion in Polish albino patients. Hum Genet 2011 2011;129:199–208. [6] Sanabria D, Groot H, Guzman J, Lattig MC. An overview of oculocutaneous albinism: TYR gene mutations in five Colombian individuals. Biomedica 2012;32:269–76 [in Spanish]. [7] Bedoya G, Garcı´a J, Montoya P, Rojas W, Ame´zquita ME, Soto I, et al. Isonymy analysis between 2 populations in Northwestern Colombia. Biomedica 2006;26:538–45 [in Spanish]. [8] Oetting WS, Pietsch J, Brott MJ, Savage S, Fryer JP, et al. The R402Q tyrosinase variant does not cause autosomal recessive ocular albinism. Am J Med Genet A 2009;149A:466–9.
3
[9] Berson JF, Frank DW, Calvo PA, Bieler BM, Marks MS. A common temperaturesensitive allelic form of human tyrosinase is retained in the endoplasmic reticulum at the nonpermissive temperature. J Biol Chem 2010;275:12281– 89. [10] Preising MN, Forster H, Gonser M, Lorenz B. Screening of TYR, OCA2, GPR143, and MC1R in patients with congenital nystagmus, macular hypoplasia, and fundus hypopigmentation indicating albinism. Mol Vis 2011;17:939–48.
Oscar Urtatiza, Diana Sanabriab, Marı´a Claudia Lattiga,* Departamento de Ciencias Biolo´gicas, Universidad de los Andes, Bogota´, DC, Colombia; bFundacio´n Contraste – Albinos por Colombia, Bogota´, DC, Colombia
a
*Corresponding author E-mail address: [email protected] (M.C. Lattig).
25 April 2014
Please cite this article in press as: Urtatiz O, et al. Oculocutaneous albinism (OCA) in Colombia: First molecular screening of the TYR and OCA2 genes in South America. J Dermatol Sci (2014), http://dx.doi.org/10.1016/j.jdermsci.2014.09.011
DESC-2739; No. of Pages 3 Journal of Dermatological Science xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of Dermatological Science journal homepage: www.jdsjournal.com
Letter to the Editor Oculocutaneous albinism (OCA) in Colombia: First molecular screening of the TYR and OCA2 genes in South America
Keywords: Oculocutaneous albinism; TYR gene; OCA2 gene; Colombia; South America
Oculocutaneous albinism (OCA) is a group of autosomal recessive disorders of the melanin biosynthesis pathway, characterized by complete lack or generalized reduction in pigmentation of hair, skin and eyes [1]. Individuals affected by OCA are at high risk of ultraviolet (UV) radiation-induced skin cancer due to the lack of photoprotective melanin. In addition, reduced visual acuity is observed mainly because early melanin precursors are vital for normal visual development in mammalian embryogenesis [2]. Genetically, seven nonsyndromic types of OCA have been described, OCA1-OCA 7 [3]. OCA1A (MIM #203100), the most common and severe form known is caused by mutations in TYR (MIM *606933) gene whereas OCA2 (MIM #203200), is a milder phenotype and the second most common type of OCA caused by mutations in OCA2 (MIM *611409) gene [4]. It is estimated that 80% of worldwide cases of OCA are explained by mutations in these two genes, TYR and OCA2, accounting for 50% and 30% cases respectively [5]. Here, we report four novel mutations and five mutations previously reported in the albinism databases, in a Colombian cohort. We analyzed 36 individuals with OCA belonging to 23 independent families from different Colombian regions. Individuals were referred by the Albino Organization ‘‘Fundacio´n Contraste – Albinos por Colombia’’. Written informed consent/assent was obtained from all participants or legal guardians. All individuals analyzed had different degrees of hypopigmentation on skin, hair and eyes, plus typical ocular landmarks of the condition representing the clinical spectrum of OCA phenotypes. Hematologic abnormalities, bleeding diathesis or deafness were absent in all individuals discarding possible syndromes such as HermanskyPudlak among others. Genomic DNA was isolated from blood sample using the kit DNA 20001 (Corpogen, Colombia). Initially, the 23 unrelated cases were screened for mutations in the coding region of TYR gene by Sanger sequencing using Macrogen service (Seoul, Republic of Korea). If either one or no mutations were found in TYR, we proceeded to sequence the coding region of OCA2 using the same platform. Mutational screening of TYR and OCA2 genes revealed 9 mutations (Table 1). Of these, 5 have been reported in the albinism databases as follows: p.D42N (rs200960909), p.G47D (rs61753180),
and p.R77Q (rs61753185) found in TYR and p.R53GfsX49 and p.A787T (rs142988897) in OCA2. Additionally, 4 novel mutations in TYR were found: two missense mutations referred as p.C55G (rs367543067) and p.C247R (rs367543068), and two nonsense mutations referred as p.S184X (rs367543066) and p.I209SfsX32. These mutations were not detected in 100 unaffected chromosomes indicating that they are likely pathogenic mutations rather than ethnic-specific polymorphisms. Family pedigrees of 3 novel mutations are shown in Fig. 1. The novel nonsense mutations S184X and I209SfsX32, both cause a stop codon in exon 1, thereby truncating tyrosinase enzyme activity. Bioinformatic analysis on the novel missense C55G and C247R mutations using SIFT and PolyPhen2 servers (December 2013), predict an impact in structure and function of the protein (SIFT score: 0; PP2 score: 1 for both mutations). Cysteine, apart from forming disulfide bridges to stabilize the native structure of the proteins is also part of the tyrosinase catalytic domain. To highlight, 11/11 individuals with homozygous or compound heterozygous mutations in TYR, have no discernible pigmentation in hair, skin and eyes (Table 1). The G47D was initially found in a small sample of 5 individuals from our population [6], here the mutation was found to be the most frequent within our study sample with 5 homozygous and 4 compound heterozygous cases. The remaining 12 individuals presented an albinism phenotype with variable degree of hypopigmentation (coloring ranges from yellow to light brown hair and from blue to brownish irides). Furthermore, when we analyzed individuals from ‘‘El Santuario and Marinilla, Antioquia’’, genetically isolated northwestern towns in Colombia well known for its high albinism prevalence [7], all were homozygous for the previously reported p.A787T mutation in OCA2 gene (OCA_24 represents all individuals from the region). Interestingly, the case OCA_14 who is native from ‘‘Samana´, Caldas’’ at 252 km on road from El Santuario, is also homozygous for the p.A787T mutation. He did not inform any family relationship to El Santuario or Marinilla, though the towns are geographically close. In 7/12 cases with variable hypopigmentation, no mutations were found in the TYR or OCA2 genes. Of these, cases OCA_8, 10, 11 and 17 were heterozygous for the frequent polymorphism p.R402Q (rs1126809) in the TYR gene. Additionally, case OCA_17 was homozygous for the polymorphism p.R305W (rs1800401) in the OCA2 gene. Also, individual OCA_22 who has one novel TYR mutation, also has the p.R305W polymorphism, whereas individual OCA_07 who also has one novel mutation in TYR presents both the p.R402Q and the p.R305W polymorphisms. These two polymorphisms (R402Q and R305W) by themselves have been reported as not sufficient to cause albinism, since unaffected individuals have been found to be homozygous for these polymorphisms [8]. In particular, the polymorphism R402Q
http://dx.doi.org/10.1016/j.jdermsci.2014.09.011 0923-1811/ß 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Urtatiz O, et al. Oculocutaneous albinism (OCA) in Colombia: First molecular screening of the TYR and OCA2 genes in South America. J Dermatol Sci (2014), http://dx.doi.org/10.1016/j.jdermsci.2014.09.011
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DESC-2739; No. of Pages 3 Letter to the Editor / Journal of Dermatological Science xxx (2014) xxx–xxx
2
Table 1 Mutational analysis in the TYR and OCA2 genes in 23 cases with OCA.
Individual code Phenotype Age Sex TYR gene
OCA2 gene
Variant 1 Nucleotide change
Aminoacid change
Variant 2 Nucleotide change
Aminoacid change
Variant 1 Nucleotide change
Aminoacid change
Variant 2 Nucleotide change
c.913C>T
p.R305W*
N.F
c.913C>T
p.R305W*
OCA_01
NP
27
F
c.140G>A
p.G47D
c.140G>A
p.G47D
–
OCA_13
NP
35
M
c.140G>A
p.G47D
c.140G>A
p.G47D
–
OCA_16
NP
52
M
c.140G>A
p.G47D
c.140G>A
p.G47D
–
OCA_19
NP
25
M
c.140G>A
p.G47D
c.140G>A
p.G47D
–
OCA_20
NP
42
F
c.140G>A
p.G47D
c.140G>A
p.G47D
–
OCA_02
NP
5
F
c.140G>A
p.G47D
c.124G>A
p.D42N
–
OCA_06
NP
30
M
c.140G>A
p.G47D
c.124G>A
p.D42N
–
OCA_21
NP
62
M
c.551C>G
p.S184X
c.140G>A
p.G47D
–
OCA_18
NP
1
F
c.580delA
p.I209SfsX32 c.140G>A
p.G47D
–
OCA_05
NP
19
F
c.163 T>G
p.C55G
c.124G>A
p.D42N
–
p.R77Q
–
Aminoacid change
OCA_12
NP
35
M
c.230G>A
p.R77Q
c.230G>A
OCA_22
VP
16
M
c.551C>G
p.S184X
N.F
OCA_07
VP
52
M
c.739T>C
p.C247R
c.1205G>A
OCA_14
VP
23
M
N.F
C.2359G>A p.A787T
C.2359G>A p.A787T C.2359G>A p.A787T
p.R402Q*
OCA_24
VP
60
M
N.F
C.2359G>A p.A787T
OCA_04
VP
21
M
N.F
c.157delA
OCA_08
VP
29
F
c.1205G>A p.R402Q*
N.F
OCA_10
VP
18
M
c.1205G>A p.R402Q*
N.F
N.F
OCA_11
VP
31
F
c.1205G>A p.R402Q*
N.F
N.F
OCA_17
VP
56
M
c.1205G>A p.R402Q*
N.F
OCA_03
VP
38
M
N.F
N.F
OCA_09
VP
27
M
N.F
N.F
OCA_15
VP
22
F
N.F
N.F
N.F
p.R53GfsX49 N.F
N.F
c.913C>T
p.R305W*
c.913C>T
p.R305W*
Novel variants are shaded gray. The OCA2 gene was not characterized in individuals with two mutations in TYR. Pathogenic polymorphisms have an asterisk. NP: no pigmentation in hair, skin and eyes; VP: variable pigmentation in hair, skin and ayes; NF: not found.
OCA_05
OCA_18
A I209SfsX32
D42N
G47D
I209SfsX32 / G47D
C55G
D42N / C55G
D42N
OCA_22
B S184X
S184X / S184X R305W
R305W
S184X / R305W
in TYR produces a thermolabile tyrosinase where at physiological temperature (37 8C) has reduced activity and is retained in the endoplasmic reticulum of melanocytes [9]. The R305W polymorphism in OCA2 has been proposed to interact with MC1R gene to explain light skin completion and visual dysfunction in Caucasian population [10]. Thus, it has been proposed that essential modifiers could explain a partial albinism phenotype [4], however until we find the genes causing albinism in these individuals it is difficult to predict how these variants may be contributing to the phenotype. In conclusion, even though our cohort is small, we have identified two novel nonsense mutations and two novel missense mutations. Individuals having two affected alleles in TYR had no discernible pigmentation in hair, skin and eyes, whereas individuals with a single affected allele showed variable degrees of hypopigmentation (Fig. 1B). We can appreciate that G47D and A787T mutations are common in Central and Northwestern regions of Colombia, respectively. Our results provide the first insights of the molecular basis of albinism in Colombia and in South America, however large-cohort studies are still needed to have a record of Colombian albinism mutations and its respective frequencies. Acknowledgements
Fig. 1. Family pedigrees of cases OCA_18, 0CA_05 and OCA_22. Arrow indicates the proband. Proband from OCA_18 inherited a novel TYR I209SfsX32 mutation from her father whereas proband from OCA_05 inherited a novel TYR C55G mutation from her mother; both cases are compound heterozygous (A, top). Proband from OCA_22 inherited the novel S184X mutation in TYR from his father and the polymorphism R305W in OCA2 from his mother. The proband and his older sister have the same variable hypopigmentation phenotype and ocular anomalies typical of OCA, however the affected sister does not have the polymorphism. Non-affected sibling also has the S184X mutation and the R305W polymorphism suggesting the presence of a second mutation in one of the other known genes or a yet unidentified gene (B, bottom).
We want to thank each one of the individuals and families who participated in this study. Special thanks to the Fundacio´n Contraste – Albinos por Colombia and to the Hospitals ‘‘San Juan de Dios’’ of Marinilla and Santuario towns. This work was supported by the Vicedecanatura de Investigaciones y Posgrados 2013, Universidad de los Andes, given to Maria Claudia Lattig and to Oscar Urtatiz.
Please cite this article in press as: Urtatiz O, et al. Oculocutaneous albinism (OCA) in Colombia: First molecular screening of the TYR and OCA2 genes in South America. J Dermatol Sci (2014), http://dx.doi.org/10.1016/j.jdermsci.2014.09.011
G Model
DESC-2739; No. of Pages 3 Letter to the Editor / Journal of Dermatological Science xxx (2014) xxx–xxx
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Oscar Urtatiza, Diana Sanabriab, Marı´a Claudia Lattiga,* Departamento de Ciencias Biolo´gicas, Universidad de los Andes, Bogota´, DC, Colombia; bFundacio´n Contraste – Albinos por Colombia, Bogota´, DC, Colombia
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*Corresponding author E-mail address: [email protected] (M.C. Lattig).
25 April 2014
Please cite this article in press as: Urtatiz O, et al. Oculocutaneous albinism (OCA) in Colombia: First molecular screening of the TYR and OCA2 genes in South America. J Dermatol Sci (2014), http://dx.doi.org/10.1016/j.jdermsci.2014.09.011
