title: Paternal or Maternal Uniparental Disomy of Chromosome 16 Resulting in Homozygosity of a Mutant Allele Causes Fanconi Anemia.
abstract: Fanconi anemia (FA) is a rare inherited disorder caused by pathogenic variants in one of 19 FANC genes. FA patients display congenital abnormalities, and develop bone marrow failure, and cancer susceptibility. We identified homozygous mutations in four FA patients and, in each case, only one parent carried the obligate mutant allele. FANCA and FANCP/SLX4 genes, both located on chromosome 16, were the affected recessive FA genes in three and one family respectively. Genotyping with short tandem repeat markers and SNP arrays revealed uniparental disomy (UPD) of the entire mutation-carrying chromosome 16 in all four patients. One FANCA patient had paternal UPD, whereas FA in the other three patients resulted from maternal UPD. These are the first reported cases of UPD as a cause of FA. UPD indicates a reduced risk of having another child with FA in the family and has implications in prenatal diagnosis.
authors: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland.
authors: Frank X
authors: FX
authors: Donovan
authors: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland.
authors: Danielle C
authors: DC
authors: Kimble
authors: Laboratory of Genome Maintenance, The Rockefeller University, New York, New York.
authors: Yonghwan
authors: Y
authors: Kim
authors: Laboratory of Genome Maintenance, The Rockefeller University, New York, New York.
authors: Francis P
authors: FP
authors: Lach
authors: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland.
authors: Ursula
authors: U
authors: Harper
authors: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland.
authors: Aparna
authors: A
authors: Kamat
authors: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland.
authors: MaryPat
authors: M
authors: Jones
authors: Laboratory of Genome Maintenance, The Rockefeller University, New York, New York.
authors: Erica M
authors: EM
authors: Sanborn
authors: Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors: Rebecca
authors: R
authors: Tryon
authors: Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors: John E
authors: JE
authors: Wagner
authors: Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
authors: Margaret L
authors: ML
authors: MacMillan
authors: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland.
authors: Elaine A
authors: EA
authors: Ostrander
authors: Human Genetics and Hematology Program, The Rockefeller University, New York, New York.
authors: Arleen D
authors: AD
authors: Auerbach
authors: Laboratory of Genome Maintenance, The Rockefeller University, New York, New York.
authors: Agata
authors: A
authors: Smogorzewska
authors: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland.
authors: Settara C
authors: SC
authors: Chandrasekharappa
mesh_terms: D000328:Adult; D002675:Child, Preschool; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005199:Fanconi Anemia / Q000235:genetics*; D052217:Fanconi Anemia Complementation Group A Protein / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D045522:Recombinases / Q000235:genetics*; D024182:Uniparental Disomy / Q000235:genetics*; D055815:Young Adult
chemical_list: C498471:FANCA protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D045522:Recombinases; C542319:SLX4 protein, human
keywords: FANCA; FANCP; Fanconi anemia; Recurrence risk; UPD16; Uniparental disomy