NDLI: Chediak-Higashi Syndrome with early Developmental Delay resulting from Paternal Heterodisomy of Chromosome 1

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Manoli, Irini Golas, Gretchen Westbroek, Wendy Vilboux, Thierry Markello, Thomas C. Introne, Wendy Maynard, Dawn Pederson, Ben Tsilou, Ekaterini Jordan, Michael B. Hart, P. Suzanne White, James G. Gahl, William A. Huizing, Marjan
Description	Country affiliation: United States Author Affiliation: Manoli I ( Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA. manolii@mail.nih.gov)
Abstract	Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease characterized by variable oculocutaneous albinism, immunodeficiency, mild bleeding diathesis, and an accelerated lymphoproliferative state. Abnormal lysosome-related organelle membrane function leads to the accumulation of large intracellular vesicles in several cell types, including granulocytes, melanocytes, and platelets. This report describes a severe case of CHS resulting from paternal heterodisomy of chromosome 1, causing homozygosity for the most distal nonsense mutation (p.E3668X, exon 50) reported to date in the LYST/CHS1 gene. The mutation is located in the WD40 region of the CHS1 protein. The patient's fibroblasts expressed no detectable CHS1. Besides manifesting the classical CHS findings, the patient exhibited hypotonia and global developmental delays, raising concerns about other effects of heterodisomy. An interstitial 747 kb duplication on 6q14.2-6q14.3 was identified in the propositus and paternal samples by comparative genomic hybridization. SNP genotyping revealed no additional whole chromosome or segmental isodisomic regions or other dosage variations near the crossover breakpoints on chromosome 1. Unmasking of a separate autosomal recessive cause of developmental delay, or an additive effect of the paternal heterodisomy, could underlie the severity of the phenotype in this patient.
File Format	HTM / HTML
ISSN	15524825
e-ISSN	15524833
DOI	10.1002/ajmg.a.33389
Journal	American Journal of Medical Genetics Part A
Issue Number	6
Volume Number	152A
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2010-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Genetics Aneuploidy Chediak-higashi Syndrome Genetics Chromosomes, Human, Pair 1 Pathology Codon, Nonsense Exons Fibroblasts Infant Lysosomes Retina Sequence Analysis, Dna Research Support, N.i.h., Extramural Research Support, N.i.h., Intramural
Content Type	Text
Resource Type	Article Case study
Subject	Genetics Genetics (clinical)

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Chediak-Higashi Syndrome with early Developmental Delay resulting from Paternal Heterodisomy of Chromosome 1

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