9q22 Deletion - First Familial Case

• Main Authors: Yamamoto Toshiyuki, Shimojima Keiko, Miikkulainen Taina, Sipponen Marjatta, Peippo Maarit, Siggberg Linda, Ignatius Jaakko, Knuutila Sakari
• Format: Article
• Language: English
• Published: BMC 2011-06-01
• Series: Orphanet Journal of Rare Diseases
• Online Access: http://www.ojrd.com/content/6/1/45

<p>Abstract</p> <p>Background</p> <p>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 <it>PTCH1 </it>gene (MIM *601309).</p> <p>Methods and Results</p> <p>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 <it>PTCH1 </it>gene, but instead 30 other gene,s including the <it>ROR2 </it>gene (MIM *602337) which causing both brachydactyly type 1 (MIM #113000) and Robinow syndrome (MIM #268310), and the immunologically active <it>SYK </it>gene (MIM *600085). The deletion in the father was <it>de novo </it>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.</p> <p>Conclusions</p> <p>This is the first report of a familial constitutional 9q22 deletion and the first deletion studied by array-CGH which does not involve the <it>PTCH1 </it>gene. The phenotype and penetrance are variable and the deletion found in the cognitively normal normal father poses a challenge in genetic counseling.</p>