An unexpected finding in a child with neurological problems: mosaic ring chromosome 18

Koç, Altuğ; Kan, Derya; Karaer, Kadri; Ergün, Mehmet Ali; Karaoğuz, Meral Yirmibeş; Gücüyener, Kıvılcım; Hinreiner, Sophie; Liehr, Thomas; Perçin, E. Ferda

doi:10.1007/s00431-007-0568-y

Cited by 13 publications

(8 citation statements)

References 22 publications

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“…P119’s karyotype was identified as 46,XX,del(18)(q21.3)/46,XX,r(18)(p11.32q21.3)/45,XX,-18, all with loss of the MBP region ( Fig 3 ). However, it has been reported that a patient with a karyotype of 45,XX,-18/46,XX,r(18)(p11.3q23)/46,XX,dicr(18)(p11.3q23;p11.3q23), which indicated a loss of MBP , showed normal brain MRI findings[ 88 ], suggesting the hypomyelination was the result of a joint effort of many genes together in the fragment lost, not only MBP. In the presenting study, besides MBP , 46,XX,del(18)(q21.3) caused the loss of 16 morbid genes including NEDD4L , MALT1 , RAX , LMAN1 , CCBE1 , MC4R , PIGN , TNFRSF11A , BCL2 , SERPINB7 , SERPINB8 , RTTN , CYB5A , TSHZ1 , CTDP1 , TXNL4A , and 46,XX,r(18)(p11.32q21.3) were caused additional loss of LPIN2 and SMCHD1 .…”

Section: Discussionmentioning

confidence: 99%

Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients

et al. 2018

PLoS ONE

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ObjectiveHypomyelinating disorders are a group of clinically and genetically heterogeneous diseases characterized by neurological deterioration with hypomyelination visible on brain MRI scans. This study was aimed to clarify the clinical and genetic features of HMDs in Chinese population.Methods119 patients with hypomyelinating disorders in Chinese population were enrolled and evaluated based on their history, clinical manifestation, laboratory examinations, series of brain MRI with follow-up, genetic etiological tests including chromosomal analysis, multiplex ligation probe amplification, Sanger sequencing, targeted enrichment-based next-generation sequencing and whole exome sequencing.ResultsClinical and genetic features of hypomyelinating disorders were revealed. Nine different hypomyelinating disorders were identified in 119 patients: Pelizaeus-Merzbacher disease (94, 79%), Pelizaeus-Merzbacher-like disease (10, 8%), hypomyelination with atrophy of the basal ganglia and cerebellum (3, 3%), GM1 gangliosidosis (5, 4%), GM2 gangliosidosis (3, 3%), trichothiodystrophy (1, 1%), Pol III-related leukodystrophy (1, 1%), hypomyelinating leukodystrophy type 9 (1, 1%), and chromosome 18q deletion syndrome (1, 1%). Of the sample, 94% (112/119) of the patients were genetically diagnosed, including 111 with mutations distributing across 9 genes including PLP1, GJC2, TUBB4A, GLB1, HEXA, HEXB, ERCC2, POLR3A, and RARS and 1 with mosaic chromosomal change of 46, XX,del(18)(q21.3)/46,XX,r(18)(p11.32q21.3)/45,XX,-18. Eighteen novel mutations were discovered. Mutations in POLR3A and RARS were first identified in Chinese patients with Pol III-related leukodystrophy and hypomyelinating leukodystrophy, respectively.SignificanceThis is the first report on clinical and genetic features of hypomyelinating disorders with a large sample of patients in Chinese population, identifying 18 novel mutations especially mutations in POLR3A and RARS in Chinese patients, expanding clinical and genetic spectrums of hypomyelinating disorders.

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Section: Discussionmentioning

confidence: 99%

Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients

et al. 2018

PLoS ONE

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“…Thus, a cryptic deletion may be the basis of the phenotypic abnormalities in apparently complete rings, such as the deletion of the IGF1R gene at 15q26.3 in a ring 15. Also, the phenotypic variability seen in patients with similar ring chromosomes may be a consequence of their instability and of the variation in gene dosage of each cell (Hecht, 1969;Palmer et al, 1977;Zuffardi et al, 1980;Knijnenburg et al, 2007;Rossi et al, 2008a), as for instance in the patient with a ring 18 reported by Koç et al (2008) who showed partial trisomy 18 in a considerable number of cells, due to the formation of dicentric rings, which resulted in a more severe phenotype. Rossi et al (2008a) described a patient with a ring 13 who had a deletion and a duplication of approximately 6 Mb each, oligohydramnios and cystic kidney, features that were attributed to trisomy 13.…”

Section: Introductionmentioning

confidence: 99%

Ring chromosome instability evaluation in six patients with autosomal rings

Sodré¹,

Guilherme²,

Meloni³

et al. 2010

Genet. Mol. Res.

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ABSTRACT. Ring chromosomes are often associated with abnormal phenotypes due to loss of genomic material and also because of ring instability at mitosis after sister chromatid exchange events. We investigated ring chromosome instability in six patients with ring chromosomes 4, 14, 15, and 18 by examining 48-and 72-h lymphocyte cultures at the first, second and subsequent cell divisions after bromodeoxyuridine incorporation. Although most cells from all patients showed only one monocentric ring chromosome, ring chromosome loss and secondary aberrations were observed both in 48-and 72-h lymphocyte cultures and in 135©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 9 (1): 134-143 (2010) Ring chromosome instability metaphase cells of the different cell generations. We found no clear-cut correlation between ring size and ring instability; we also did not find differences between apparently complete rings and rings with genetic material loss. The cytogenetic findings revealed secondary aberrations in all ring chromosome patients. We concluded that cells with ring chromosome instability can multiply and survive in vivo, and that they can influence the patient's phenotype.

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“…In general, clinical phenotypes of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications, ring instability and level of mosaicism [ 6 , 7 ]; also, loss of ring chromosomes may lead for some chromosomes to mosaic karyotypes with 45 chromosomes [ 14 ]. The proband under report presented with primary observation of small head size and facial dysmorphism.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization and evaluation of complex rearrangements in a case of ring chromosome 15

et al. 2017

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BackgroundRing chromosome 15 is a rare genetic entity. Only a few cases have been reported with characterization using molecular techniques. The clinical presentation is quite variable, as a result of differences in the breakpoints, haploinsufficiency of genes involved in deleted segment/s, level of mosaicism and ring instability resulting in a variability of rearrangement of genetic material.Case presentationThe proband, a 2 months old boy, presented with small head size and facial dysmorphism. On examination microcephaly, triangular face, small anterior frontanelle, micrognathia, hypotonia, unilateral simian crease, hypertelorism, umbilical hernia, micropenis with mild phimosis were noted. Karyotype revealed 46,XY,r(15)(p11.2q26). Array-comparative genomic hybridization (aCGH) and targeted gene sequencing for microcephaly was carried out for genotype phenotype correlation. Array-CGH detected a 2.8 Mb terminal deletion at 15q26.3 along with a 496 kb interstitial micro-duplication, encompassing the IGF1R gene, in the affected genomic region, which was otherwise missed on conventional karyotype.ConclusionThe present study highlights the importance of aCGH in not only delineating specific phenotypes through accurate genotypic correlation but also in detection and evaluation of ring chromosome with unexpected complex rearrangements.Electronic supplementary materialThe online version of this article (10.1186/s13039-017-0339-z) contains supplementary material, which is available to authorized users.

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An unexpected finding in a child with neurological problems: mosaic ring chromosome 18

Cited by 13 publications

References 22 publications

Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients

Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients

Ring chromosome instability evaluation in six patients with autosomal rings

Molecular characterization and evaluation of complex rearrangements in a case of ring chromosome 15

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