title: 9q22 Deletion--first familial case.
abstract: BACKGROUND
  Only 29 cases of constitutional 9q22 deletions have been published and all have been sporadic. Most associate with Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS, MIM #109400) due to haploinsufficiency of the PTCH1 gene (MIM *601309).
  
  
  RESULTS
  We report two mentally retarded female siblings and their cognitively normal father, all carrying a similar 5.3 Mb microdeletion at 9q22.2q22.32, detected by array CGH (244 K). The deletion does not involve the PTCH1 gene, but instead 30 other gene,s including the ROR2 gene (MIM *602337) which causing both brachydactyly type 1 (MIM #113000) and Robinow syndrome (MIM #268310), and the immunologically active SYK gene (MIM *600085). The deletion in the father was de novo and FISH analysis of blood lymphocytes did not suggest mosaicism. All three patients share similar mild dysmorphic features with downslanting palpebral fissures, narrow, high bridged nose with small nares, long, deeply grooved philtrum, ears with broad helix and uplifted lobuli, and small toenails. All have significant dysarthria and suffer from continuous middle ear and upper respiratory infections. The father also has a funnel chest and unilateral hypoplastic kidney but the daughters have no malformations.
  
  
  CONCLUSIONS
  This is the first report of a familial constitutional 9q22 deletion and the first deletion studied by array-CGH which does not involve the PTCH1 gene. The phenotype and penetrance are variable and the deletion found in the cognitively normal normal father poses a challenge in genetic counseling.
authors.affiliation: Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 3, 00014 Helsinki, Finland. linda.siggberg@helsinki.fi
authors.forename: Linda
authors.initials: L
authors.lastname: Siggberg
authors.forename: Maarit
authors.initials: M
authors.lastname: Peippo
authors.forename: Marjatta
authors.initials: M
authors.lastname: Sipponen
authors.forename: Taina
authors.initials: T
authors.lastname: Miikkulainen
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Jaakko
authors.initials: J
authors.lastname: Ignatius
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
mesh_terms: D000328:Adult; D057215:Body Dysmorphic Disorders; D002675:Child, Preschool; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics; D000072377:Syk Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C000606896:SYK protein, human; D000072377:Syk Kinase