Case Report Smallest critical region for microcephaly in a patient with mosaic ring chromosome 13

Abstract

ABSTRACT. A ring chromosome 13 or r(13) exhibits breakage and reunion at breakage points on the long and short arms of chromosome 13, with deletions of the chromosomal segments distal to the breakage points. The r(13) chromosome accounts for approximately 20% of ring chromosomes compatible with life. We describe a female patient with mental retardation, growth retardation, microcephaly, craniofacial dysmorphy, hearing impairment, and prolonged prothrombin time. Chromosomal analysis via GTG banding of peripheral blood lymphocy tes revealed a karyotype of 46,XX,r (13) (109,743,110,721)]. A cytogenetic study of peripheral blood revealed a rare chromosomal abnormality associated with different cell lines that included structural and numerical abnormalities of chromosome 13. This case, along with 14 previously reported cases, indicate that the smallest critical region for chromosome 13 microcephaly is 109,743,729-144,110,721.

Molecular and Cytogenetic Evaluation of a Patient with Ring Chromosome 13 and Discordant Results

“…With the exception of the 2 cases reported by Guilherme et al [2011], in which duplications of 43.5 and 1.5 Mb were found, the corresponding microarray analysis in vivo has been mostly limited to delineation of the terminal 13q deletion even among cases where dynamic mosaicism was evident by using cytogenetic techniques Su et al, 2013]. This is of particular interest given the potential phenotypic consequences of not only the resulting deletion, as is typically assumed for ring chromosomes, but also of the associated duplication [Rossi et al, 2008;Guilherme et al, 2011].…”

“…The clinical severity of the described ring 13 syndrome is broad and influenced by the stability of the ring as well as the extent and the breakpoints of the deletions along chromosome 13 [Brandt et al, 1992;Guilherme et al, 2011;Su et al, 2013]. Consistently observed features of ring 13 include growth failure, microcephaly, cognitive deficits, and facial dysmorphism, with occasional reports of genital abnormalities, anal atresia, cardiac defects, eye malformations, skeletal anomalies, epilepsy, and hearing loss [Brandt et al, 1992;Bedoyan et al, 2004;Liao et al, 2011;Su et al, 2013].…”

“…Consistently observed features of ring 13 include growth failure, microcephaly, cognitive deficits, and facial dysmorphism, with occasional reports of genital abnormalities, anal atresia, cardiac defects, eye malformations, skeletal anomalies, epilepsy, and hearing loss [Brandt et al, 1992;Bedoyan et al, 2004;Liao et al, 2011;Su et al, 2013].…”

Towards New Approaches to Evaluate Dynamic Mosaicism in Ring Chromosome 13 Syndrome

“…Ring chromosomes originate from the break and rejoining of both chromosome arms and consequently formation of a circular rearrangement, most o en with a genetic loss of the extremities. Ring Chromosome 13 is observed in around 20% of ring cases in still-births and its prevalence is estimated in 1/58,000 births [1,2]. Clinical ndings seem associated with the size of the rings, concerning the extent of deleted segments, but also on the ring instability, which results in more severe features [3][4][5][6][7][8][9].…”

“…Studies of genotype-phenotype correlation delineate the 13q-syndrome and thus provide an e ective understanding of that clinical entity [2,[12][13][14][15][16][17]. Identi cation of speci c genes and their respective association to clinical traits has led, for instance, to the establishment of ZIC2 as a hallmark in cases of 13q-, due to the fact that this gene loss is causative of holoprosencephaly [18].…”