title: Two genes are responsible for Griscelli syndrome at the same 15q21 locus.
abstract: Griscelli syndrome is a rare autosomal recessive disease characterized by pigment dilution, variable cellular immunodeficiency, and an acute phase of uncontrolled T lymphocyte and macrophage activation. We previously mapped the disease locus to 15q21 and showed that a MyoVa gene (HGMW-approved symbol MYO5A) defect leads to Griscelli syndrome. We report a second MyoVa mutation in a new patient, confirming this first finding. However, in four other Griscelli syndrome patients analyzed, the MYOVA protein is expressed, and no mutation can be detected in the MyoVa gene coding sequence, even in the alternatively spliced region for which exon-intron boundaries were characterized. Linkage analysis performed in 15 Griscelli families thus far studied confirms the first localization. However, fine haplotype analysis in three families strongly suggests the existence of a second gene at the same locus for Griscelli syndrome less than 7.3 cM distant from the MyoVa gene.
authors.affiliation: Unité de Recherches sur le développement normal et pathologique du système immunitaire, INSERM U429, Hôpital Necker Enfants Malades, 149 rue de Sèvres, Paris Cedex 15, 75743, France.
authors.forename: E
authors.initials: E
authors.lastname: Pastural
authors.forename: F
authors.initials: F
authors.lastname: Ersoy
authors.forename: N
authors.initials: N
authors.lastname: Yalman
authors.forename: N
authors.initials: N
authors.lastname: Wulffraat
authors.forename: E
authors.initials: E
authors.lastname: Grillo
authors.forename: F
authors.initials: F
authors.lastname: Ozkinay
authors.forename: I
authors.initials: I
authors.lastname: Tezcan
authors.forename: G
authors.initials: G
authors.lastname: Gediköglu
authors.forename: N
authors.initials: N
authors.lastname: Philippe
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: G
authors.initials: G
authors.lastname: de Saint Basile
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002675:Child, Preschool; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005808:Genes, Recessive; D008040:Genetic Linkage; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D017496:Hypopigmentation / Q000235:genetics*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000172:deficiency / Q000235:genetics* / Q000302:isolation & purification; D008213:Lymphocyte Activation / Q000235:genetics; D008262:Macrophage Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D018995:Myosin Heavy Chains; D024701:Myosin Type V; D009422:Nervous System Diseases / Q000235:genetics; D013045:Species Specificity; D013577:Syndrome
chemical_list: D007381:Intermediate Filament Proteins; C513082:Myo5a protein, mouse; C077511:MYO5A protein, human; D024701:Myosin Type V; D018995:Myosin Heavy Chains