Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypopigmentation disorders that are associated with immunodeficiency feature both partial albinism of hair, skin and eyes together with leukocyte defects. These disorders include Chediak Higashi (CHS), Griscelli (GS), Hermansky-Pudlak (HPS) and MAPBP-interacting protein deficiency syndromes. These are heterogeneous autosomal recessive conditions in which the causal genes encode proteins with specific roles in the biogenesis, function and trafficking of secretory lysosomes. In certain specialized cells, these organelles serve as a storage compartment. Impaired secretion of specific effector proteins from that intracellular compartment affects biological activities. In particular, these intracellular granules are essential constituents of melanocytes, platelets, granulocytes, cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Thus, abnormalities affect pigmentation, primary hemostasis, blood cell counts and lymphocyte cytotoxic activity against microbial pathogens. Among eight genetically distinct types of HPS, only type 2 is characterized by immunodeficiency. Recently, a new subtype, HPS9, was defined in patients presenting with immunodeficiency and oculocutaneous albinism, associated with mutations in the pallidin-encoding gene, PLDN.Hypopigmentation together with recurrent childhood bacterial or viral infections suggests syndromic albinism. T and NK cell cytotoxicity are generally impaired in patients with these disorders. Specific clinical and biochemical phenotypes can allow differential diagnoses among these disorders before molecular testing. Ocular symptoms, including nystagmus, that are usually evident at birth, are common in patients with HPS2 or CHS. Albinism with short stature is unique to MAPBP-interacting protein (MAPBPIP) deficiency, while hemophagocytic lymphohistiocytosis (HLH) mainly suggests a diagnosis of CHS or GS type 2 (GS2). Neurological disease is a long-term complication of CHS, but is uncommon in other syndromic albinism. Chronic neutropenia is a feature of HPS2 and MAPBPIP-deficiency syndrome, whereas it is usually transient in CHS and GS2. In every patient, an accurate diagnosis is required for prompt and appropriate treatment, particularly in patients who develop HLH or in whom bone marrow transplant is required. This review describes the molecular and pathogenetic mechanisms of these diseases, focusing on clinical and biochemical aspects that allow early differential diagnosis.
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PMID:Clinical, laboratory and molecular signs of immunodeficiency in patients with partial oculo-cutaneous albinism. 2413 93

Oculocutaneous albinism (OCA), which is roughly divided into non-syndromic and syndromic OCA, is a group of autosomal recessive disorders caused by mutations in genes associated with pigmentation. Patients with OCA have hypopigmentation and ocular manifestations such as photophobia, amblyopia, and nystagmus. Hermansky-Pudlak syndrome (HPS), the most common syndromic OCA, is characterized by the additional features of a bleeding tendency and other critical systemic comorbidities such as pulmonary fibrosis and immunodeficiency. NGS-based gene analyses have identified several new causative genes for OCA and have detected rare subtypes of OCA with high accuracy including Japanese patients. In our survey of 190 Japanese OCA patients/families, OCA4 is the most common subtype (25.3%) followed by OCA1 (20.0%), HPS1 (14.7%), and OCA2 (8.4%). Similar to the A481T variant in OCA2, which is associated with a mild form of OCA2 and skin color variation, the c.-492_489delAATG variant located in the promoter region of SLC45A2 has been uniquely identified in Japanese patients with a mild form of OCA4. Further, rare OCA subtypes, including OCA3, HPS2, HPS3, HPS4, HPS5, HPS6, and HPS9, have also been identified in Japanese patients. The clinical characteristics and underlying molecular mechanisms of each subtype of OCA are concisely summarized in this review.
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PMID:Current landscape of Oculocutaneous Albinism in Japan. 3296 95