title: Acute lymphoblastic leukemia in a patient with Greig cephalopolysyndactyly and interstitial deletion of chromosome 7 del(7)(p11.2 p14) involving the GLI3 and ZNFN1A1 genes.
abstract: Greig cephalopolysyndactyly (GCPS; OMIM 175700) is an autosomal dominant condition caused by mutations of the gene GLI3, located on 7p13. To date, several cases of deletions and/or translocations involving this locus have been reported in patients with GCPS. GLI3 is a transcription factor from the GLI-Kruppel gene family that has been implicated in three distinct entities: GCPS, Pallister-Hall syndrome, and postaxial polydactyly type A. The zinc finger protein, subfamily 1, member 1 gene (ZNFN1A1; OMIM 603023), on 7p12, codes for a lymphoid-restricted zinc finger transcription factor, ZNFN1A1, also called IKAROS, that regulates lymphocyte differentiation and has been associated with the development of childhood leukemia. We present the case of a 9-year-old Latin-American boy who was referred for stem cell transplantation because of recurrent acute lymphoblastic leukemia (ALL). On evaluation, he was found to have dysmorphic features consistent with GCPS, including a prominent forehead, down-slanting palpebral fissures, 1-2-3 toe syndactyly, broad thumbs and first toes, and mild developmental delay. He had developed ALL at 5 years of age. Chromosome analysis of bone marrow and fibroblastic cells showed an interstitial deletion of chromosome arm 7p, del(7)(p11.2p14), in 74% and 44% of the cells, respectively. We performed FISH analysis with a BAC clone containing the ZNFN1A1 gene and demonstrated that it is contained in the deleted segment. To our knowledge, this is the first report of a patient with GCPS and leukemia. We hypothesize that constitutional deletion of the ZNFN1A1 gene in this patient may have resulted in an increased risk of lymphoid malignancy.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mendoza-Londono
authors.forename: Catherine D
authors.initials: CD
authors.lastname: Kashork
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
authors.forename: Robert
authors.initials: R
authors.lastname: Krance
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Plon
mesh_terms: D001854:Bone Marrow Cells / Q000473:pathology; D002648:Child; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D051740:Ikaros Transcription Factor; D007621:Karyotyping; D051741:Kruppel-Like Transcription Factors; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D013576:Syndactyly / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000074290:Zinc Finger Protein Gli3
chemical_list: D004268:DNA-Binding Proteins; C065683:GLI3 protein, human; C497239:IKZF1 protein, human; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D000074290:Zinc Finger Protein Gli3; D051740:Ikaros Transcription Factor