title: Chediak-Higashi syndrome associated with maternal uniparental isodisomy of chromosome 1.
abstract: Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder (incidence around 1 in 106 births), characterised by a complex immunologic defects, reduced pigmentation, and presence of giant granules in many different cell types. It most likely results from defective organellar trafficking or protein sorting. The causative gene (LYST) has recently been identified and shown to be homologous to the beige locus in the mouse. CHS has always been reported associated with premature-termination-codon mutations in both alleles of LYST. We report a unique patient with CHS, who was homozygous for a stop codon in the LYST gene on chromosome 1 and who had a normal 46,XY karyotype. The mother was found to be a carrier of the mutation, whereas the father had two normal LYST alleles. Non-paternity was excluded by the analysis of microsatellite markers from different chromosomes. The results of 13 informative microsatellite markers spanning the entire chromosome 1 revealed that the proband had a maternal isodisomy of chromosome 1 encompassing the LYST mutation. The proband's clinical presentation also confirms the absence of imprinted genes on chromosome 1.
authors.affiliation: Unité de Recherches sur le développement normal et pathologique du système immunitaire INSERM U429, Hôpital Necker-Enfants Malades.
authors.forename: R
authors.initials: R
authors.lastname: Dufourcq-Lagelouse
authors.forename: N
authors.initials: N
authors.lastname: Lambert
authors.forename: M
authors.initials: M
authors.lastname: Duval
authors.forename: G
authors.initials: G
authors.lastname: Viot
authors.forename: E
authors.initials: E
authors.lastname: Vilmer
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: M
authors.initials: M
authors.lastname: Prieur
authors.forename: G
authors.initials: G
authors.lastname: de Saint Basile
mesh_terms: D000483:Alleles; D002609:Chediak-Higashi Syndrome / Q000235:genetics*; D002648:Child; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002878:Chromosomes, Human, Pair 1; D005220:Fathers; D005260:Female; D005808:Genes, Recessive; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008957:Models, Genetic; D009035:Mothers; D010375:Pedigree; D011506:Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033921:Vesicular Transport Proteins
chemical_list: D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; C102161:LYST protein, human; C491133:Lyst protein, mouse; D011506:Proteins; D033921:Vesicular Transport Proteins