De novo 13q12.3-q14.11 deletion involving BRCA2 gene in a patient with developmental delay, elevated IgM levels, transient ataxia, and cerebellar hypoplasia, mimicking an A-T like phenotype.
We report on a child with a de novo deletion of approximately 12 Mb detected through array comparative genomic hybridization (CGH). The deletion involved chromosome bands 13q12.3-13q14.11 and determined the loss of ≥50 genes. A second deletion on chromosome 12p11.3p11.22 of 43-167 kb, including about 12 genes, was unlikely of clinical relevance because inherited from the asymptomatic father. The child had developmental delay, dysmorphisms, and many features reminiscent of ataxia-telangiectasia (A-T), as cerebellar ataxia, oculocutaneus telangiectasia, and recurrent upper airway infections. Atraumatic fractures of the metatarsus were noted. Moreover, this is a rare case of 13q deletion syndrome associated with peripheral blood white cells radiosensitivity to bleomycin, reminiscent of what previously reported on X-ray hypersensitivity of fibroblasts from patients with alterations of this chromosome. The immunological evaluation revealed increased IgM serum levels and a low proliferative response to mitogens, PHA, and CD3 cross-linking (CD3 XL). After 12 years of age only a mild dysmetria persisted, while the proliferative response to mitogens became normal by 9 years of age.
Department of Pediatrics, "Federico II" University, Naples, Italy.
Emilia
E
Cirillo
Rosa
R
Romano
Alfonso
A
Romano
Giuliana
G
Giardino
Anne
A
Durandy
Lucio
L
Nitsch
Rita
R
Genesio
Eleonora
E
Di Gregorio
Simona
S
Cavalieri
Giovanna
G
Abate
Luigi
L
Del Vecchio
Alfredo
A
Brusco
Claudio
C
Pignata
D000293:Adolescent; D001259:Ataxia / Q000235:genetics / Q000473:pathology; D002531:Cerebellum / Q000002:abnormalities / Q000473:pathology; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics* / Q000276:immunology; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics / Q000473:pathology; D024522:Genes, BRCA2; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009421:Nervous System Malformations / Q000235:genetics / Q000473:pathology; D010641:Phenotype
D007075:Immunoglobulin M