Novel case of dup(3q) syndrome due to a de novo interstitial duplication 3q24-q26.31 with minimal overlap to the dup(3q) critical region.
Dup(3q) syndrome is characterized by typical facial features, mental and growth retardation, often with congenital heart defects. The syndrome has attracted special attention because of the clinical overlap with Cornelia de Lange syndrome (CDLS). Patients with dup(3q) syndrome are trisomic for segments of the long arm of chromosome 3, most often within the region 3q21 to 3qter. Most cases have arisen as unbalanced translocations and do involve other chromosomes also. A dup(3q) minimal region has been defined at 3q26.3-q27. We report here a 15-month-old boy with a de novo interstitial inverted duplication of 3q24-q26.31. Clinical evaluation revealed mild but typical features of dup(3q) syndrome. The duplication was characterized by conventional and molecular cytogenetics. The results allow further narrowing of the dup(3q) critical region at its distal end and suggest the existence of one or several major genes responsible for the dup(3q) syndrome in the proximal half of 3q26.31. Moreover, the results of fluorescence in situ hybridization (FISH) analysis with BAC probes suggest a disruption of the NLGN1 gene at the distal end of the duplication in 3q26.31 in the patient. The breakpoint within NLGN1 is unique for this patient, and the contribution of NLGN1 disruption to the phenotype of this patient remains unclear. Yet since NLGN1 is involved in synaptogenesis in the central nervous system, altered gene dosage is a good candidate for mental retardation as a recurrent feature of dup(3q) syndrome.
Meins
Moritz
M
Department of Human Genetics, Ruhr-University Bochum, Germany. moritz.meins@rub.de
Hagh
Javad Karimzad
JK
Gerresheim
Fritz
F
Einhoff
Elisabeth
E
Olschewski
Heidi
H
Strehl
Henning
H
Epplen
Jörg T
JT
D002869:Chromosome Aberrations; D002871:Chromosome Banding; D025063:Chromosome Disorders / Q000235:genetics* / Q000473:pathology; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D020440:Gene Duplication; D006330:Heart Defects, Congenital / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000473:pathology; D007621:Karyotyping; D008297:Male; D013577:Syndrome