Smith-Magenis syndrome and Moyamoya disease in a patient with del(17)(p11.2p13.1).
Chromosomal rearrangements causing microdeletions and microduplications are a major cause of congenital malformation and mental retardation. Because they are not visible by routine chromosome analysis, high resolution whole-genome technologies are required for the detection and diagnosis of small chromosomal abnormalities. Recently, array-comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) have been useful tools for the identification and mapping of deletions and duplications at higher resolution and throughput. Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome caused by deletion or mutation of the retinoic acid induced 1 (RAI1) gene and is often associated with a chromosome 17p11.2 deletion. We report here on the clinical and molecular analysis of a 10-year-old girl with SMS and moyamoya disease (occlusion of the circle of Willis). We have employed a combination of aCGH, FISH, and MLPA to characterize an approximately 6.3 Mb deletion spanning chromosome region 17p11.2-p13.1 in this patient, with the proximal breakpoint within the RAI1 gene. Further, investigation of the genomic architecture at the breakpoint intervals of this large deletion documented the presence of palindromic repeat elements that could potentially form recombination substrates leading to unequal crossover.
Girirajan
Santhosh
S
Department of Human Genetics, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA.
Mendoza-Londono
Roberto
R
Vlangos
Christopher N
CN
Dupuis
Lucie
L
Nowak
Norma J
NJ
Bunyan
David J
DJ
Hatchwell
Eli
E
Elsea
Sarah H
SH
D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D009072:Moyamoya Disease / Q000150:complications* / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques; D009693:Nucleic Acid Hybridization; D011995:Recombination, Genetic; D012097:Repressor Proteins; D013577:Syndrome
D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D012097:Repressor Proteins