Chediak–Higashi syndrome: description of two novel homozygous missense mutations causing divergent clinical phenotype

• DOI: 10.1111/ejh.12203
• Publication Date: 2013-10-11T23:43:56Z
• Authors: Isabel Sánchez‐Guiu; Ana I. Antón; Nuria García‐Barberá; José Navarro‐Fern...; Constantino Martínez; Jose L. Fuster; Jose M. Couselo; Francisco J. Ortuño; Vicente Vicente; Jose Rivera; Maria L. Lozano
• Keywords: Mutant protein

Abstract Chediak– H igashi syndrome ( CHS ) is a rare autosomal recessive disease resulting from mutations in the LYST / 1 gene, which encodes for 429 kD protein, 1/ , that regulates vesicle trafficking and determines size of lysosomes other organelles. To date, 60 different have been characterized, reasonably straightforward phenotype–genotype correlation has suggested. We describe two patients on opposite ends clinical spectrum with novel missense mutations. characterized these terms their mutations, protein localization expression, mRNA stability, electrostatic potential. Patient first report severe early‐onset homozygous mutation (c.11362 G > A p. 3725 R CHS1 gene. This molecular change results reduction at level, not due to an effect, but maybe consequence both, structure most likely attributable remarkable serious perturbation 2, who exhibited adolescence form disease, was found be c.961 T C 258 seemed minor effect protein. Reexamining accepted premises mutant alleles being reported among clinically mild forms disorder should carried out, attempts link genotype phenotype require identifying actual mutation. Early accurate diagnosis severity extremely important early differentiate would benefit premature enrollment into transplantation protocol.