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.

La sindrome di Chediak-Higashi a esordio tardivo

2021 ◽  
Vol 24 (4) ◽  
pp. 118-123
Author(s):  
Silvia Ciancia ◽  
Maria Francesca Dalla Porta ◽  
Greta Miriam Cingolani ◽  
Monica Cellini ◽  
Annarosa Soresina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bacterial Infections ◽  
Autosomal Recessive Disorder ◽  
Clinical History ◽  
Oculocutaneous Albinism ◽  
Gene Encoding ◽  
Atypical Form ◽  
Neurological Alterations ◽  
Chediak Higashi Syndrome ◽  
Classic Form

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder caused by mutations in the CHS1/LYST gene, encoding for LYST protein, involved in lysosomal trafficking. It is characterized by recurrent bacterial infections, oculocutaneous albinism, silver hair, haematological and neurological alterations and a possible evolution towards the socalled accelerated phase (haemophagocytic lymphohistiocytosis). It is classified in a classic form, with infantile onset, lethal if bone marrow transplantation is not promptly performed, and in an atypical form, with adolescent/adult onset, for which a more conservative approach may be possible. The paper describes a case of hypertrophic-hyperplastic gingivopathy associated with leuko-neutropenia. The evaluation of the bone marrow smear raised the suspicion of CHS and the analysis of the clinical history highlighted the presence of suggestive criteria for atypical CHS. The genetic investigation confirmed the diagnosis.

scholarly journals Two Novel Mutations Identified in an African-American Child with Chediak-Higashi Syndrome

2010 ◽  
Vol 2010 ◽  
pp. 1-4 ◽  
Author(s):  
Kerry Morrone ◽  
Yanhua Wang ◽  
Marjan Huizing ◽  
Elie Sutton ◽  
James G. White ◽  
...  
Keyword(s):  
African American ◽  
Late Onset ◽  
High Serum ◽  
Neurological Dysfunction ◽  
Chromosome 1 ◽  
Laboratory Evaluation ◽  
African American Child ◽  
American Child ◽  
Nonsense Mutations ◽  
Chediak Higashi Syndrome

Background.Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive disorder characterized by oculocutaneous albinism, immunodeficiency, coagulopathy and late-onset, progressive neurological dysfunction. It also has an “accelerated phase” characterized by hemophagocytic lymphohistiocytosis (HLH). The disease is caused by mutations in theCHS1/LYSTgene located on chromosome 1, which affects lysosome morphology and function. We report the case of an African-American child with CHS in Case. This 16-month old African-American girl presented with fever and lethargy. The proband had pale skin compared to her parents, with light brown eyes, silvery hair and massive hepatosplenomegaly. Her laboratory evaluation was remarkable for pancytopenia, high serum ferritin and an elevated LDH. Bone marrow aspirate revealed large inclusions in granulocytes and erythrophagocytosis consistent with HLH. Genetic evaluation revealed two novel nonsense mutations in theCHS1gene: c.3622C>T(p.Q1208X) and c.11002G>T(p.E3668X).Conclusions.Our patient is one of the few cases of CHS reported in the African American population. We identified 2 nonsense mutations in theCHS1gene, the first mutation analysis published of an African-American child with Chediak-Higashi Syndrome. These two mutations predict a severe phenotype and thus identification of these mutations has an important clinical significance in CHS.

scholarly journals Mutational Analysis of Oculocutaneous Albinism: A Compact Review

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Balu Kamaraj ◽  
Rituraj Purohit
Keyword(s):  
Autosomal Recessive ◽  
Mutational Analysis ◽  
Autosomal Recessive Disorder ◽  
Oculocutaneous Albinism ◽  
Melanin Production ◽  
Melanin Biosynthesis ◽  
Molecular Features ◽  
New Genes ◽  
Pigment Accumulation ◽  
Severe Type

Oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by either complete lack of or a reduction of melanin biosynthesis in the melanocytes. The OCA1A is the most severe type with a complete lack of melanin production throughout life, while the milder forms OCA1B, OCA2, OCA3, and OCA4 show some pigment accumulation over time. Mutations in TYR, OCA2, TYRP1, and SLC45A2 are mainly responsible for causing oculocutaneous albinism. Recently, two new genes SLC24A5 and C10orf11 are identified that are responsible to cause OCA6 and OCA7, respectively. Also a locus has been mapped to the human chromosome 4q24 region which is responsible for genetic cause of OCA5. In this paper, we summarized the clinical and molecular features of OCA genes. Further, we reviewed the screening of pathological mutations of OCA genes and its molecular mechanism of the protein upon mutation byin silicoapproach. We also reviewed TYR (T373K, N371Y, M370T, and P313R), OCA2 (R305W), TYRP1 (R326H and R356Q) mutations and their structural consequences at molecular level. It is observed that the pathological genetic mutations and their structural and functional significance of OCA genes will aid in development of personalized medicine for albinism patients.

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 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.

Chediak-Higashi syndrome is not due to a defect in microtubule-based lysosomal mobility

1993 ◽  
Vol 106 (1) ◽  
pp. 99-107 ◽  
Author(s):  
C.M. Perou ◽  
J. Kaplan
Keyword(s):  
Motor System ◽  
Autosomal Recessive ◽  
Phorbol Esters ◽  
Autosomal Recessive Disorder ◽  
Diagnostic Feature ◽  
Vesicle Formation ◽  
Cytoplasmic Ph ◽  
Intracellular Vesicle ◽  
Murine Homolog ◽  
Chediak Higashi Syndrome

Chediak-Higashi Syndrome is an autosomal recessive disorder that affects intracellular vesicle formation. The diagnostic feature of Chediak-Higashi Syndrome is the presence of ‘giant’ lysosomes clustered near the nucleus. Lysosome morphology in macrophages is maintained by microtubules and microtubule-based motors, such as kinesin. Dramatic changes in lysosome morphology can be induced by lowering cytoplasmic pH or by adding phorbol esters. When macrophages from beige mice (a murine homolog of Chediak-Higashi Syndrome) were subjected to these protocols they were able to alter their lysosomal distribution and morphology to the same degree as macrophages from control mice. These results indicate that lysosomes in Chediak cells are capable of interacting with the microtubule-based motor system, suggesting that the defective gene product is not an altered microtubular element involved in lysosomal movement.

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 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. 

Three Cases of Joubert Syndrome in a Consanguineous Syrian Family and a Interesting Case of Multinational Collaboration

2021 ◽  
Author(s):  
Davor Petrović ◽  
Vida Čulić ◽  
Zofia Swinderek-Alsayed
Keyword(s):  
Low Income ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Joubert Syndrome ◽  
Interesting Case ◽  
Low Income Countries ◽  
Ocular Motor ◽  
Quality Health Care ◽  
Quality Health ◽  
Motor Apraxia

AbstractJoubert syndrome (JS) is a rare congenital, autosomal recessive disorder characterized by a distinctive brain malformation, developmental delay, ocular motor apraxia, breathing abnormalities, and high clinical and genetic heterogeneity. We are reporting three siblings with JS from consanguineous parents in Syria. Two of them had the same homozygous c.2172delA (p.Trp725Glyfs*) AHI1 mutation and the third was diagnosed prenatally with magnetic resonance imaging. This pathogenic variant is very rare and described in only a few cases in the literature. Multinational collaboration could be of benefit for the patients from undeveloped, low-income countries that have a low-quality health care system, especially for the diagnosis of rare diseases.

A Case of Congenital Glucose Galactose Malabsorption with a New Mutation in the SLC5A1 Gene

2020 ◽  
Author(s):  
Hasan Akduman ◽  
Dilek Dilli ◽  
Serdar Ceylaner
Keyword(s):  
Mutation Analysis ◽  
Autosomal Recessive ◽  
Glucose Transporter ◽  
Neonatal Period ◽  
Autosomal Recessive Disorder ◽  
Homozygous Mutation ◽  
New Mutation ◽  
Early Neonatal Period ◽  
Sodium Dependent ◽  
Hypernatremic Dehydration

AbstractCongenital glucose-galactose malabsorption (CGGM) is an autosomal recessive disorder originating from an abnormal transporter mechanism in the intestines. It was sourced from a mutation in the SLC5A1 gene, which encodes a sodium-dependent glucose transporter. Here we report a 2-day-old girl with CGGM who presented with severe hypernatremic dehydration due to diarrhea beginning in the first hours of life. Mutation analysis revealed a novel homozygous mutation NM_000343.3 c.127G > A (p.Gly43Arg) in the SLC5A1 gene. Since CGGM can cause fatal diarrhea in the early neonatal period, timely diagnosis of the disease seems to be essential.

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