scholarly journals Prospective Study of the Phenotypic and Mutational Spectrum of Ocular Albinism and Oculocutaneous Albinism

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 508
Author(s):  
Hwei Wuen Chan ◽  
Elena R. Schiff ◽  
Vijay K. Tailor ◽  
Samantha Malka ◽  
Magella M. Neveu ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Autosomal Recessive ◽  
Oculocutaneous Albinism ◽  
Whole Genome ◽  
Ocular Albinism ◽  
Panel Testing ◽  
Hereditary Disorders ◽  
Foveal Hypoplasia ◽  
Hermansky Pudlak Syndrome ◽  
Chediak Higashi Syndrome

Albinism encompasses a group of hereditary disorders characterized by reduced or absent ocular pigment and variable skin and/or hair involvement, with syndromic forms such as Hermansky–Pudlak syndrome and Chédiak–Higashi syndrome. Autosomal recessive oculocutaneous albinism (OCA) is phenotypically and genetically heterogenous (associated with seven genes). X-linked ocular albinism (OA) is associated with only one gene, GPR143. We report the clinical and genetic outcomes of 44 patients, from 40 unrelated families of diverse ethnicities, with query albinism presenting to the ocular genetics service at Moorfields Eye Hospital NHS Foundation Trust between November 2017 and October 2019. Thirty-six were children (≤ 16 years) with a median age of 31 months (range 2–186), and eight adults with a median age of 33 years (range 17–39); 52.3% (n = 23) were male. Genetic testing using whole genome sequencing (WGS, n = 9) or a targeted gene panel (n = 31) gave an overall diagnostic rate of 42.5% (44.4% (4/9) with WGS and 41.9% (13/31) with panel testing). Seventeen families had confirmed mutations in TYR (n = 9), OCA2, (n = 4), HPS1 (n = 1), HPS3 (n = 1), HPS6 (n = 1), and GPR143 (n = 1). Molecular diagnosis of albinism remains challenging due to factors such as missing heritability. Differential diagnoses must include SLC38A8-associated foveal hypoplasia and syndromic forms of albinism.

scholarly journals Genetic testing for ocular albinism and oculocutaneous albinism

2017 ◽  
Vol 1 (s1) ◽  
pp. 80-82
Author(s):  
Andi Abeshi ◽  
Carla Marinelli ◽  
Tommaso Beccari ◽  
Munis Dundar ◽  
Benedetto Falsini ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Clinical Utility ◽  
Autosomal Recessive ◽  
Scientific Literature ◽  
Genetic Test ◽  
Autosomal Recessive Inheritance ◽  
Oculocutaneous Albinism ◽  
Ophthalmological Examination ◽  
Recessive Inheritance ◽  
Ocular Albinism

Abstract We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for ocular albinism and oculocutaneous albinism. Ocular albinism has X-linked recessive inheritance, with a prevalence that varies from 1/40000 to 1/1000000, and is caused by mutations in the GPR143 and CACNA1F genes. Oculocutaneous albinism has autosomal recessive inheritance, with an overall prevalence of 1/17000, and is caused by mutations in the TYR, OCA2, TYRP1, SLC45A2, SLC24A5 and C10orf11 genes. Clinical diagnosis involves ophthalmological examination, testing of visually evoked potentials (VEP) and electrophysiological testing (ERG). The genetic test is useful for confirming diagnosis, differential diagnosis, for couple risk assessment and access to clinical trials.

Hermansky-Pudlak Syndrome and Chediak-Higashi Syndrome: Disorders of Vesicle Formation and Trafficking

2001 ◽  
Vol 86 (07) ◽  
pp. 233-245 ◽  
Author(s):  
Marjan Huizing ◽  
Yair Anikster ◽  
William Gahl
Keyword(s):  
Autosomal Recessive ◽  
Dense Body ◽  
Oculocutaneous Albinism ◽  
Clinical Findings ◽  
Vesicle Formation ◽  
Platelet Storage ◽  
A Subunit ◽  
Hermansky Pudlak Syndrome ◽  
Chediak Higashi Syndrome ◽  
Golgi Network

SummaryThe rare autosomal recessive metabolic disorders Hermanky-Pudlak syndrome (HPS) and Chediak-Higashi syndrome (CHS) share the clinical findings of oculocutaneous albinism and a platelet storage pool deficiency. In addition, HPS exhibits ceroid lipofuscinosis and CHS is characterized by infections and an accelerated phase. The two disorders result from defects in vesicles of lysosomal lineage. Of the two known HPS-causing genes, HPS1 has no recognizable function, while ADTB3A codes for a subunit of an adaptor complex responsible for new vesicle formation from the trans-Golgi network. Other HPS-causing genes are likely to exist. The only known CHS-causing gene, LYST, codes for a large protein of unknown function. In general, HPS appears to be a disorder of vesicle formation and CHS a defect in vesicle trafficking. These diseases and their variants mirror a group of mouse hypopigmentation mutants. The gene products involved will reveal how the melanosome, platelet dense body, and lysosome are formed and trafficked within cells.

scholarly journals Novel HeterogenousCHS1Mutations Identified in Five Japanese Patients with Chediak-Higashi Syndrome

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Fuminori Tanabe ◽  
Hirotake Kasai ◽  
Michiko Morimoto ◽  
Shigeharu Oh ◽  
Hidetoshi Takada ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Japanese Patients ◽  
Visual Disturbance ◽  
Oculocutaneous Albinism ◽  
Neurological Dysfunction ◽  
Nonsense Mutations ◽  
Chediak Higashi Syndrome ◽  
Exon 10

Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive disorder characterized by oculocutaneous albinism, recurrent bacterial infections and progressive neurological dysfunction. We demonstrate novel heterogenous mutations ofCHS1, the responsive gene of CHS, identified in five Japanese patients with CHS. Patients 1, 2, and 3 were siblings, and they had albinism of the skin and hair. They all had a heterogenous two-base deletion (c.5541-5542 del AA, p.Q1847fsX1850) in exon 18. Patient 4 had a heterogenous single-base insertion (c.3944-3945 ins C, p.T1315fsX1331) in exon 10. The patient exhibited severe early-onset phenotype and suffered from hemophagocytic lymphohistiocytosis. Patient 5 had two heterogenous nonsense mutations; c.7982C>G, p.S2661X in exon 30 and c.8281A>T, p.R2761X in exon 31. The patient suffered from infections in childhood and had visual disturbance and albinism of the skin and hair. TheCHS1mutations described here have not been reported previously.

scholarly journals Chédiak-Higashi syndrome: presentation of seven cases

1998 ◽  
Vol 116 (6) ◽  
pp. 1873-1878 ◽  
Author(s):  
Eugénia Maria Grilo Carnide ◽  
Cristina Miuki Abe Jacob ◽  
Antonio Carlos Pastorino ◽  
Raquel Bellinati-Pires ◽  
Maria Beatriz Guimarães Costa ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Infectious Complications ◽  
Oculocutaneous Albinism ◽  
Recurrent Infections ◽  
Laboratory Findings ◽  
Public Care ◽  
Cytoplasmic Granules ◽  
Allergy And Immunology ◽  
Chediak Higashi Syndrome ◽  
Rare Autosomal Recessive Disease

CONTEXT: Chédiak-Higashi Syndrome (CHS) is a rare autosomal recessive disease characterized by recurrent infections, giant cytoplasmic granules, and oculocutaneous albinism. OBJECTIVE: To describe clinical and laboratory findings from CHS patients. DESIGN: Case report. SETTING: The patients were admitted into the Allergy and Immunology Unit of the Instituto da Criança, a tertiary public care institution. CASES REPORT: Seven patients had oculocutaneous albinism, recurrent infections and giant cytoplasmic granules in the leukocytes. One patient had low IgG levels and three showed impaired bactericidal activity of neutrophils. Six patients died of infectious complications during the accelerated phase. Therapy included ascorbic acid and antibiotics. Chemotherapy was used for the accelerated phase in two patients. Bone marrow transplantation (BMT) was proposed for one patient. DISCUSSION: The authors emphasize the need for early diagnosis and therapy of CHS. BMT should be indicated before the accelerated phase of the disease has developed.

Genetic Testing of a Puerto Rican Family Trio with Oculocutaneous Albinism Type 1B Reveals a Misdiagnosis of Hermansky‐Pudlak Syndrome

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Joseline Serrano ◽  
Ingrid M. Montes ◽  
Jessicca Y. Renta ◽  
Ricardo Rojas ◽  
Carmen L. Cadilla
Keyword(s):  
Genetic Testing ◽  
Puerto Rican ◽  
Oculocutaneous Albinism ◽  
Family Trio ◽  
Hermansky Pudlak Syndrome

scholarly journals Clinical and genetic variability in children with partial albinism

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Patrick Campbell ◽  
Jamie M. Ellingford ◽  
Neil R. A. Parry ◽  
Tracy Fletcher ◽  
Simon C. Ramsden ◽  
...  
Keyword(s):  
Molecular Diagnosis ◽  
Diagnostic Yield ◽  
Skin Pigmentation ◽  
Diagnostic Challenge ◽  
Ocular Albinism ◽  
Functional Polymorphisms ◽  
Panel Testing ◽  
Gene Panel Testing ◽  
Significant Enrichment ◽  
Foveal Hypoplasia

Abstract Individuals who have ocular features of albinism and skin pigmentation in keeping with their familial background present a considerable diagnostic challenge. Timely diagnosis through genomic testing can help avert diagnostic odysseys and facilitates accurate genetic counselling and tailored specialist management. Here, we report the clinical and gene panel testing findings in 12 children with presumed ocular albinism. A definitive molecular diagnosis was made in 8/12 probands (67%) and a possible molecular diagnosis was identified in a further 3/12 probands (25%). TYR was the most commonly mutated gene in this cohort (75% of patients, 9/12). A disease-causing TYR haplotype comprised of two common, functional polymorphisms, TYR c.[575 C > A;1205 G > A] p.[(Ser192Tyr);(Arg402Gln)], was found to be particularly prevalent. One participant had GPR143-associated X-linked ocular albinism and another proband had biallelic variants in SLC38A8, a glutamine transporter gene associated with foveal hypoplasia and optic nerve misrouting without pigmentation defects. Intriguingly, 2/12 individuals had a single, rare, likely pathogenic variant in each of TYR and OCA2 – a significant enrichment compared to a control cohort of 4046 individuals from the 100,000 genomes project pilot dataset. Overall, our findings highlight that panel-based genetic testing is a clinically useful test with a high diagnostic yield in children with partial/ocular albinism.

scholarly journals Increased use of genetic health care in Iceland 2012-2017

2022 ◽  
Vol 108 (01) ◽  
pp. 11-16
Author(s):  
Hákon Björn Högnason ◽  
◽  
Vigdís Fjóla Stefánsdóttir ◽  
Eirný Þöll Þórólfsdóttir ◽  
Jón Jóhannes Jónsson ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Genetic Counselling ◽  
Single Gene ◽  
Gene Panel ◽  
Whole Genome ◽  
Panel Testing ◽  
Gene Testing ◽  
Time Period ◽  
Whole Exome ◽  
Gene Panel Testing

INTRODUCTION: A genetic counselling unit at Landspitali hospital (LSH) was established in 2006. Meanwhile, genetic testing has become an integral part of general health care. In this article we detail the outcome of genetic testing at the Department of Genetic and Molecular Medicine (DGM) at Landspitali over a five year period (2012-2017). Factors that were analyzed for the time period were: Number of patients, reason for referral, reason for genetic testing without genetic counselling and yield (proportion of positive tests) of genetic testing. METHODS: Data was analysed from two medical record databases, Shire and Saga, used by the DGM in the time period. RESULTS: The number of individuals coming for genetic counselling increased every year over the time period. Reasons for referral were cancer-related in two-thirds of cases. Other reasons for referral included various other familial disorders. Most common were autosomal dominant disorders like myotonic dystrophy, hypertrophic cardiomyopathy and autosomal recessive disorders like spinal muscular atrophy (SMA) and GM1-gangliosidosis. Most common reasons for genetic testing outside of the LSH GC unit was because of managable diseases like hemochromatosis and F5/Prothrombin-related thrombophilia. Yield of genetic testing was assessed for a) known mutation testing / carrier testing, b) single gene testing, c) gene panel testing and d) whole genome and whole exome sequencing. Known mutation testing was positive in 33% of cases and single gene testing in 46% of cases. The yield of gene panel testing for cancer was found to be lower (20%) than gene panel testing for other disorders (40%). The yield of whole exome and whole genome sequencing was 46%.

Therapy refractory menorrhagia as first manifestation of Hermansky-Pudlak syndrome

2011 ◽  
Vol 31 (S 01) ◽  
pp. S61-S63
Author(s):  
S. Gehrisch ◽  
J. T. Tauer ◽  
R. Knöfler ◽  
J. Lohse
Keyword(s):  
Body Weight ◽  
Case Report ◽  
Clinical Response ◽  
Autosomal Recessive ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Single Injection ◽  
Oculocutaneous Albinism ◽  
Function Defect ◽  
Hermansky Pudlak Syndrome

Summary Introduction Oculocutaneous albinism (OCA) in combination with a platelet function defect caused by a disturbed release reaction from platelet δ-granules (storage pool defect – SPD) is typical for the autosomal recessive inherited Hermansky-Pudlak syndrome (HPS). Case report A girl (age: 13 years) with OCA was hospitalized with transfusion-requiring menorrhagia. The suspicion of HPS was confirmed by results of lumi-aggregometry. Suspecting a disorder in primary haemostasis treatment with tranexamic acid (10 mg/kg body weight every 8 h i. v.), desmopressin (0.3 μg/kg body weight every 8 to 12 h) and hormonal therapy (norethisterone) was started but the menorrhagia persisted. Clinical response was finally achieved by a single injection of 100 μg/kg body weight recombinant factor VIIa (rFVIIa). Conclusion The diagnosis of HPS should be suspected in patients with OCA and bleeding symptoms and is confirmed by the proof of SPD. In case of absent clinical response to desmopressin the application of rFVIIa should be considered. Hormones and antifibrinolytics are useful options in the treatment of extensive menorrhagia.

scholarly journals Chediak Higashi syndrome presenting in accelerated phase: a case report and literature review

2017 ◽  
Vol 4 (4) ◽  
pp. 1537
Author(s):  
SHRAVANI M. R. ◽  
Murali B. H. ◽  
Chandrakala Chandrakala ◽  
Chaitra Chaitra ◽  
Varshini Varshini
Keyword(s):  
Clinical Characteristics ◽  
Autosomal Recessive ◽  
Blood Smear ◽  
Hair Analysis ◽  
Peripheral Blood Smear ◽  
Oculocutaneous Albinism ◽  
Bleeding Diathesis ◽  
Lysosomal Disorder ◽  
Chediak Higashi Syndrome ◽  
Spleen And Lymph Nodes

Chediak Higashi syndrome (CHS) is a rare autosomal recessive lysosomal disorder characterized by frequent infections, oculocutaneous albinism, bleeding diathesis and progressive neurologic deterioration. In 85% of cases, CHS patients develop the accelerated phase characterized by pancytopenia, high fever, and lymphohistiocytic infiltration of liver, spleen, and lymph nodes. Treatment of accelerated-phase CHS is difficult and the prognosis is poor. Here, we report a case of CHS in a 1-year-old girl who presented in the accelerated phase of the disease. CHS diagnosis was made on the basis of clinical characteristics, hair analysis and identification of pathognomonic giant azurophilic granules in peripheral blood smear. 

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