Newborn Screening for Hermansky-Pudlak Syndrome Type 3 in Puerto Rico

Torres-Serrant, Maribel; Ramirez, Sonia I.; Cadilla, Carmen L.; Ramos-Valencia, Gilberto; Santiago-Borrero, Pedro J.

doi:10.1097/mph.0b013e3181e5e1f1

Cited by 14 publications

(8 citation statements)

References 18 publications

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“…Torres and co-workers 24 found that type 3 HPS has an average carrier frequency of 1:85 among Puerto Rican newborns. Our study demonstrated a higher frequency of patients harboring the clinical findings associated to the HPS1 had poorer BCVA, higher incidence of esotropia, total iris transillumination, translucent maculae, and several color deficiencies.…”

Section: Discussionmentioning

confidence: 99%

Ocular Findings in Patients with the Hermansky-Pudlak Syndrome (Types 1 and 3)

Jardón

Izquierdo

Renta

et al. 2014

Ophthalmic Genetics

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Purpose To describe and compare ocular findings in patients with Hermansky-Pudlak syndrome (HPS) type 1 and 3. Methods This is a retrospective case series of 64 patients with HPS from 1999 to 2009 evaluated at an outpatient private ophthalmologic clinic. Patients underwent genetic analysis of selected albinism (Tyrosine and P gene) and HPS genes (HPS-1 and HPS-3) by screening for common mutations and exon sequencing with DNA screening. Descriptive and a non-parametric statistical analysis were done. Results Nearly 70% of the patients were homozygous for common Puerto Rican mutations leading to the HPS1 gene (16-BP DUP, 53.6%), while 30% had the 3904-BP DEL HPS3 gene mutation. BCVA was poorer in patients with type 1 HPS than in patients with type 3 HPS (p<0.001), esotropia was more common among type 1 HPS (p<0.018), while exotropia was more common among patients with type 3 HPS. Total iris transillumination was more common in patients with type 1 HPS and minimal iris transillumination in patients with type 3 HPS (p<0.001). The maculae were translucent in patients with type 1 HPS, while patients with type 3 HPS had opaque maculae (p<0.001). Conclusions Patients with type 1 HPS had poorer BCVA, increase incidence of esotropia, lighter iris and macular appearance. In contrast, patients with type 3 HPS 3 had more exotropia. In addition, to our knowledge this is the largest series type 3 HPS ever reported.

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Section: Discussionmentioning

confidence: 99%

Ocular Findings in Patients with the Hermansky-Pudlak Syndrome (Types 1 and 3)

Jardón

Izquierdo

Renta

et al. 2014

Ophthalmic Genetics

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“…Two separate founder mutations in the HPS1 (10q23) and HPS3 (3q24) genes associated with the Hermansky-Pudlak syndrome have been identified on the island. 14-16 The p.G47D (11q14) mutation associated with Type I-A oculocutaneous albinism in Puerto Rico appeared to have originated from a common founder. 17 In addition, the p.R457Q (11p11) substitution is a common mutation in Puerto Rico and is linked to the otherwise extremely rare genetic prothrombin deficiency disorder.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of a Loss-of-Function Mutation in the Proton-Coupled Folate Transporter Gene (PCFT-SLC46A1) Causing Hereditary Folate Malabsorption in Puerto Rico

Mahadeo

Diop-Bove

Ramirez

et al. 2011

The Journal of Pediatrics

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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.

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“…One in 14,000 individuals of central Puerto Rican descent are estimated to be homozygous for this deletion. The carrier frequency in central Puerto Rico is ~1:32 (Santiago Borrero et al, 2006) and 1:85 in all of Puerto Rico (Torres‐Serrant et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…The worldwide prevalence of HPS is estimated to be 1–9/1,000,000 (Christensen et al, 2017; Huizing et al, 2000). A few ethnic founder variants occur in HPS genes, in particular in northwest region of Puerto Rico, an estimated 400 individuals are affected (~1/1,800 affected; carrier frequency 1:21) and carry a homozygous 16‐bp duplication in HPS1 (c.1472_1487dup16‐bp; Table 3; Santiago Borrero et al, 2006; Witkop et al, 1990), and in Central Puerto Rico a 3.9‐kb deletion in HPS3 (NM_032383.5(HPS3):c.‐2993_217+692del; Table 5) has an estimated population prevalence of ~1/4,000 (carrier frequency 1:32) in (Anikster et al, 2001; Santiago Borrero et al, 2006; Torres‐Serrant et al, 2010). Other founder variants without frequency estimates have been reported and are discussed elsewhere in this report for each HPS subtype (S. Ito et al, 2005; Oh et al, 1998; Schallreuter et al, 1993; Schreyer‐Shafir et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Hermansky–Pudlak syndrome: Mutation update

et al. 2020

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Hermansky-Pudlak syndrome (HPS) is a group of 10 autosomal recessive multisystem disorders, each defined by the deficiency of a specific gene. HPS-associated genes encode components of four ubiquitously expressed protein complexes: Adaptor protein-3 (AP-3) and biogenesis of lysosome-related organelles complex-1 (BLOC-1) through -3. All individuals with HPS exhibit albinism and a bleeding diathesis; additional features occur depending on the defective protein complex. Pulmonary fibrosis is associated with AP-3 and BLOC-3 deficiency, immunodeficiency with AP-3 defects, and gastrointestinal symptoms are more prevalent and severe in BLOC-3 deficiency. Therefore, identification of the HPS subtype is valuable for prognosis, clinical management, and treatment options. The prevalence of HPS is estimated at 1-9 per 1,000,000. Here we summarize 264 reported and novel variants in 10 HPS genes and estimate that~333 Puerto Rican HPS subjects and~385 with other ethnicities are reported to date. We provide pathogenicity predictions for missense and splice site variants and list variants with high minor allele frequencies. Current cellular and clinical aspects of HPS are also summarized. This review can serve as a manifest for molecular diagnostics and genetic counseling aspects of HPS.

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Newborn Screening for Hermansky-Pudlak Syndrome Type 3 in Puerto Rico

Cited by 14 publications

References 18 publications

Ocular Findings in Patients with the Hermansky-Pudlak Syndrome (Types 1 and 3)

Ocular Findings in Patients with the Hermansky-Pudlak Syndrome (Types 1 and 3)

Prevalence of a Loss-of-Function Mutation in the Proton-Coupled Folate Transporter Gene (PCFT-SLC46A1) Causing Hereditary Folate Malabsorption in Puerto Rico

Hermansky–Pudlak syndrome: Mutation update

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