Clinical, cytogenetic, and molecular characterization of six patients with ring chromosomes 22, including one with concomitant 22q11.2 deletion.
We report here on six patients with a ring chromosome 22 and the range of cytogenetic and phenotypic features presented by them. Genomic analysis was carried out using classical and molecular cytogenetics, MLPA (Multiplex Ligation-dependent Probe Amplification) and genome-wide SNP-array analysis. The ring was found in all patients, but Patient 6 displayed constitutional mosaicism with a normal cell line. Five patients had deletions in the ring chromosome 22, and in four of them the breakpoints--unique for each patient--could be identified by genome-wide SNP-array analysis. One patient presented with a 22q11.2 deletion concomitant with the deletion caused by the ring formation. Common phenotypic features included autism, speech delay and seizures, as previously reported for individuals with r(22) and/or 22q13.3 deletions. Investigation of the genes within the deletions revealed multiple genes related to development of the central nervous system, psychomotor delay, severe language impairment, hypotonia, and autistic symptoms. There was no clear correlation between the severity of clinical features and the size of the deleted segment. This study underscores the variability in ring structure and clinical presentation of the r(22) and adds information to the limited literature on this rare disorder.
Genetics Division, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil.
Roberta Santos
RS
Guilherme
Karina Cunha
KC
Soares
Milena
M
Simioni
Tarsis Paiva
TP
Vieira
Vera Lúcia
VL
Gil-da-Silva-Lopes
Chong Ae
CA
Kim
Décio
D
Brunoni
Nancy Bettina
NB
Spinner
Laura Kathleen
LK
Conlin
Denise Maria
DM
Christofolini
Leslie Domenici
LD
Kulikowski
Carlos Eduardo
CE
Steiner
Maria Isabel
MI
Melaragno
D000293:Adolescent; D002648:Child; D002871:Chromosome Banding; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010641:Phenotype; D012303:Ring Chromosomes
22q11.2 deletion; 22q13 deletion; ring chromosome 22; speech delay and SNP array