Molecular and clinical delineation of the 17q22 microdeletion phenotype.
Deletions involving 17q21-q24 have been identified previously to result in two clinically recognizable contiguous gene deletion syndromes: 17q21.31 and 17q23.1-q23.2 microdeletion syndromes. Although deletions involving 17q22 have been reported in the literature, only four of the eight patients reported were identified by array-comparative genomic hybridization (array-CGH) or flourescent in situ hybridization. Here, we describe five new patients with 1.8-2.5-Mb microdeletions involving 17q22 identified by array-CGH. We also present one patient with a large karyotypically visible deletion involving 17q22, fine-mapped to ~8.2 Mb using array-CGH. We show that the commonly deleted region in our patients spans 0.24 Mb and two genes; NOG and C17ORF67. The function of C17ORF67 is not known, whereas Noggin, the product of NOG, is essential for correct joint development. In common with the 17q22 patients reported previously, the disease phenotype of our patients includes intellectual disability, attention deficit hyperactivity disorder, conductive hearing loss, visual impairment, low set ears, facial dysmorphology and limb anomalies. All patients displayed NOG-related bone and joint features, including symphalangism and facial dysmorphology. We conclude that these common clinical features indicate a novel clinically recognizable, 17q22 contiguous microdeletion syndrome.
1] Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden [2] Department of Molecular Medicine and Surgery and Center of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden [3] Department of Hand Surgery, Södersjukhuset, Stockholm, Sweden.
Tobias
T
Laurell
Johanna
J
Lundin
Britt-Marie
BM
Anderlid
Jerome L
JL
Gorski
Giedre
G
Grigelioniene
Samantha J L
SJ
Knight
Ana C V
AC
Krepischi
Agneta
A
Nordenskjöld
Susan M
SM
Price
Carla
C
Rosenberg
Peter D
PD
Turnpenny
Angela M
AM
Vianna-Morgante
Ann
A
Nordgren
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D016366:Open Reading Frames; D010641:Phenotype; D013577:Syndrome; D000099176:Noggin Protein
D002352:Carrier Proteins; D000099176:Noggin Protein