FISH‐mapping of telomeric 14q32 deletions: Search for the cause of seizures

Abstract

Ring chromosome 14 is a rare cytogenetic disorder. Individuals with r(14) generally have developmental delay and seizures. Other features include hypotonia, microcephaly, mild facial dysmorphism, and retinal pigmentation. Most of these features are also found in patients with linear terminal deletions of chromosome 14, except for seizures and retinal abnormalities. The objective of the study was to determine if deletion of a specific chromosome region is a possible explanation for the occurrence of seizures in patients with ring chromosome 14. Patients diagnosed either with r(14) (six patients) or a deletion of distal 14q (three patients) were analyzed by FISH (fluorescence in situ hybridization) with BAC probes. We observed differences in the size of deletions in the studied group. In two r(14) patients, we did not detect any deletion; the four other patients had deletions of various sizes, ranging from 0.8 Mb to 5 Mb. Two linear deletions were 3.2 Mb and 5.3 Mb in length, respectively; the third case had an interstitial deletion that did not overlap with the others. The deleted regions in ring chromosomes showed overlap with those in the two linear terminal deletions. We conclude that there is unlikely to be a specific deleted locus in 14q32.3 that predisposes r(14) patients to seizures or retinal pigmentation. The cause is probably related to the formation of the ring itself and the effect this may have on local chromatin structure.

Ring 14 chromosome presenting as early‐onset isolated partial epilepsy

“…Schlade-Bartusiak et al 24 compared the characteristic features of ring 14 syndrome (seizure, hypotonia, developmental delay, retinal pigmentation, microcephaly, dysmorphic facies) in six children with ring 14 chromosomes and three children with telomeric 14q32 deletions without the formation of a ring chromosome. The children with telomeric deletions and those with ring 14 chromosomes had similar features, except for seizures and retinal abnormalities.…”

Molecular cytogenetic characterization of terminal 14q32 deletions in two children with an abnormal phenotype and corpus callosum hypoplasia

“…Five cases were diagnosed only by subtelomere fluorescent in situ hybridisation (FISH). 3,20,21 If we consider the case of Maurin et al, 10 a pure distal 14q deletion since the presence of a terminal NOR region should not have any influence on the phenotype assuming the absence of position effect, a total of eight cases with pure distal deletion were confirmed by FISH 12,17,19,20,21 and the break points were mapped in only four patients 10,12,19,20 (Table 1).…”

Terminal 14q Deletion and Duplication with Gastrointestinal and Pulmonary Disease

“…Chromosome 14q abnormalities have been associated with various clinical features including inconsistent gastrointestinal and respiratory defects [7][8][9][10][11][12][13][14][15][16][17][18][19]. Phenotypic variability can be attributed to differences in size of the 14q rearrangment, an additional chromosomal abnormality or the parental origin of the additional 14q segment [20][21][22].…”

“…Atresias (anal, esophageal and tracheoesophageal), imperforate anus, midgut malrotation, intestinal dysmotility, pyloric stenosis and laryngomalacia have been identified but there is no consistent phenotype with 14q aberrations [4,8,[12][13][14][15][16]. Terminal deletion 14q and duplication 14q in a patient with neonatal hypotonia, psychomotor retardation, intellectual disabilities, short stature and facial dysmorphism has been reported [17].…”