Hermansky-Pudlak syndrome (HPS) (MIM #203300) is a heterogeneous group of autosomal recessive disorders characterized by oculocutaneous albinism (OCA), bleeding tendency, and lysosomal dysfunction. HPS is very common in Puerto Rico (PR), particularly in the northwest part of the island, with a frequency of approximately 1:1,800. Two HPS genes and mutations have been identified in PR, a 16-base pair (bp) duplication in HPS1 and a 3,904-bp deletion in HPS3. In Puerto Ricans with more typical OCA, the most common mutation of the tyrosinase (TYR) (human tyrosinase (OCA1) gene) gene was G47D. We describe screening 229 Puerto Rican OCA patients for these mutations, and for mutations in the OCA2 gene. We found the HPS1 mutation in 42.8% of cases, the HPS3 deletion in 17%, the TYR G47D mutation in 3.0%, and a 2.4-kb deletion of the OCA2 gene in 1.3%. Among Puerto Rican newborns, the frequency of the HPS1 mutation is highest in northwest PR (1:21; 4.8%) and lower in central PR (1:64; 1.6%). The HPS3 gene deletion is most frequent in central PR (1:32; 3.1%). Our findings provide insights into the genetics of albinism and HPS in PR, and provide the basis for genetic screening for these disorders in this minority population.

Objective To determine whether subjects of Puerto Rican heritage are at increased risk for a specific mutation of the proton-coupled folate transporter (PCFT) causing hereditary folate malabsorption (HFM). Study design Three percent of the births in Puerto Rico in 2005, with additional regional oversampling, were screened for the prevalence of the c.1082G>A; p.Y362_G389 del PCFT gene mutation. Six new subjects of Puerto Rican heritage with the clinical diagnosis of HFM were also assessed for this mutation. Results Six subjects of Puerto Rican heritage with the clinical diagnosis of HFM were all homozygous for the c.1082G>A; p.Y362_G389 del PCFT mutation. Three heterozygote carriers were identified from the 1582 newborn samples randomly selected from births in Puerto Rico in 2005. The carrier frequency for the mutated allele was 0.2% island-wide and 6.3% in Villalba. Conclusion These findings are consistent with a common mutation in the PCFT gene causing HFM that has disseminated to Puerto Ricans who have migrated to mainland United States. Because prompt diagnosis and treatment of infants with HFM can prevent the consequences of this disorder, newborn screening should be considered in high-risk populations and physicians should be aware of its prevalence in infants of Puerto Rican ancestry.

Background: Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive disorder characterized by albinism, mucocutaneous bleeding, and storage of ceroid material in macrophages (Hermansky and Pudlak, 1959). Many of these patients develop pulmonary fibrosis and colitis from which about 68% eventually die (Witkop et al, 1990). Patients that are not easily identified by physical characteristics (mostly HPS-3 patients) may have serious hemorrhagic complications when suffer severe injuries or surgical interventions. HPS is a rare disease worldwide, but it is the most common single-gene disorder among persons of Puerto Rican descent (Witkop et al, 1990). Two founder mutations (HPS-1 and HPS-3) account for most HPS cases in Puerto Rico (PR). The first one is widely prevalent in the Northwestern region (Oh et al, 1996) and the other (HPS-3) appeared in a small mid-central region of the island (Anikster et al,2000). HPS-3 patients usually present minimal skin pigmentation deficiency and thus diagnosis of albinism often is missed. Visual acuity problems often are detected late in infancy and childhood. This usually results in poor school progress, late diagnosis and treatment of patients, and delayed counseling of parents. Objective: To determine the prevalence of HPS-3 in Puerto Rican (PR) newborns using DNA pooling technique. Design/Methods: An aleatory sample of 4,690 PR infants born in 2005 (representing approximately 10% of annual PR births) was tested for the HPS-3 mutation, using DNA extracted from dried blood samples (Drocopoli et al, 1996). PCR analysis was carried out as described (Oh et al, 1996; Anikster et al,2000). Samples were tested in DNA pools of 5 newborns each. The validation of the PCR pooling technique for HPS-3 had been carried out in earlier studies in our laboratory by testing 1,500 newborn dried blood samples individually and in 300 total 5-sample pools. All positive samples detected individually were also unequivocally identified as positive when tested in pools. Results: Among the 4,690 newborns tested, 56 presented the HPS-3 mutation and they were confirmed in repeated testing. Two newborns were found to be HPS-3 homozygous. This finding was confirmed several times. The HPS-3 carrier frequency in the island-wide newborn population was 1:84 (1.19%). Both homozygous infants were born close to but outside of the high prevalence region previously reported in PR (Anikster et al,2001). Forty five percent of infants heterozygous for the HPS-3 mutation and one homozygous were found in the high prevalence area and the surrounding 10 miles radius; the other 56% of cases were distributed throughout the rest of the island. Conclusions: Our study has shown that the high prevalence area previously described by Anikster et al, where the founder mutation was identified has been spreading out throughout the rest of the island. Apparently, this is the result of rapid mobility of the Puerto Rican population during the last decades. Our data also demonstrate that the relatively high prevalence of the HPS-3 mutation (1.19%) justifies universal newborn screening. The use of DNA pooling reduces time and labor in newborn screening thus facilitating early diagnosis and treatment of children with HPS-3 and the provision of genetic counseling to patient’s parents and relatives.

Background Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive disorder characterized by albinism, mucocutaneous bleeding, and storage of ceroid material in macrophages1. Patients that are not easily identified by physical characteristics (mostly HPS-3 patients) may have hemorrhagic complications with trauma or surgery. Objective To determine the prevalence of HPS-3 in Puerto Rican newborns using DNA pooling technique. Design/Methods Twelve percent of annual Puerto Rican births were tested randomly by PCR for the HPS-3 mutation, using pooled DNA extracted from dried blood samples. Results HPS-3 mutation was detected in 75 samples. Two newborns were found to be homozygous. Carrier frequency was 1:85 (1.18%). Conclusions The HPS-3 carrier frequency found (1.18%) justifies universal newborn screening in Puerto Rico. DNA pooling reduces time and labor in newborn screening thus facilitating early diagnosis and treatment of children with HPS-3 and the provision of genetic counseling to parents and relatives.