Paternal uniparental disomy chromosome 14‐like syndrome due a maternal de novo 160 kb deletion at the 14q32.2 region not encompassing the IG‐ and the MEG3‐DMRs: Patient report and genotype–phenotype correlation

Corsello, Giovanni; Salzano, Emanuela; Vecchio, Davide; Antona, Vincenzo; Grasso, Marina; Malacarne, Michela; Carella, Massimo; Palumbo, Pietro; Piro, Ettore; Giuffrè, Mario

doi:10.1002/ajmg.a.37293

Cited by 17 publications

(16 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While preparing this manuscript, three additional microdeletions were reported that did not include the DMRs, like in our family A. 16,17 As visualized in Figure 3, there is no smallest region of overlap common to all 13 microdeletions. It is therefore likely that several regulatory mechanisms can be disrupted at different positions within the 14q32.2 chromosomal region with a similar clinical outcome.…”

Section: Discussionmentioning

confidence: 82%

“…To our knowledge, 13 patients with a UPD (14)pat phenotype caused by a maternal 14q32 deletion have been reported. [3][4][5]16,17 The precise localization of these is depicted in Figure 3. The clinical characteristics of all deletion carriers, including the cases described here are summarized in Table 1.…”

Section: Discussionmentioning

confidence: 99%

“…It is therefore likely that several regulatory mechanisms can be disrupted at different positions within the 14q32.2 chromosomal region with a similar clinical outcome. It is generally accepted that aberrant expression of the maternally Kagami et al 3 Kagami et al 4 Beygo et al 5 Corsello et al 16 Rosenfeld et al transcribed copies of MEG3, MEG8 or RTL1aseither through the disruption of the imprinting control centers IG-DMR and MEG3-DMR or through direct disruption of the genes by a deletion has a crucial role in the pathogenesis of KOS14, although an effect of other regulatory sequences cannot be excluded. Little is known about the function of the long non-coding RNAs -MEG3 and MEG8.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Novel microdeletions on chromosome 14q32.2 suggest a potential role for non-coding RNAs in Kagami-Ogata syndrome

et al. 2016

View full text Add to dashboard Cite

In approximately 20% of individuals with Kagami-Ogata syndrome (KOS14, MIM 608149), characterized by a bell-shaped thorax with coat-hanger configuration of the ribs, joint contractures, abdominal wall defects and polyhydramnios during the pregnancy, the syndrome is caused by a maternal deletion of the imprinted gene cluster in chromosome 14q32.2. Most deletions reported so far included one or both of the differentially methylated regions (DMRs) - DLK1/MEG3 IG-DMR and MEG3-DMR. We present two unrelated families with two affected siblings each, presenting with classical KOS14 due to maternally inherited microdeletions. Interestingly, all four patients have lived through to adulthood, even though mortality rates for patients with KOS14 due to a microdeletion are relatively high. In the first family, none of the DMRs is included in the deletion and the methylation status is identical to that of controls. Deletions that do not encompass the DMRs in this region are thus sufficient to elicit the full KOS14 phenotype. In the second family, a partially overlapping deletion including both DMRs and MEG3 was detected. In summary, we show that patients with KOS14 can live into adulthood, that causal deletions do not have to include the DMRs and that consequently a normal methylation pattern does not exclude KOS14.

show abstract

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Novel microdeletions on chromosome 14q32.2 suggest a potential role for non-coding RNAs in Kagami-Ogata syndrome

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Indeed, these last deleterious effects have been found to be more frequently related to the LRPPRC A354V founder mutation, responsible for an increased mitochondrial vulnerability and nutrient-induced cytotoxicity [ 12 ]. Moreover, different dose effects could also result from functional differences in gene expression depending on the parental origin of the single mutation, as recently described in other neurodevelopmental disorders [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Novel LRPPRC compound heterozygous mutation in a child with early-onset Leigh syndrome French-Canadian type: case report of an Italian patient

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background Mitochondrial diseases, also known as oxidative phosphorylation (OXPHOS) disorders, with a prevalence rate of 1:5000, are the most frequent inherited metabolic diseases. Leigh Syndrome French Canadian type (LSFC), is caused by mutations in the nuclear gene (2p16) leucine-rich pentatricopeptide repeat-containing (LRPPRC). It is an autosomal recessive neurogenetic OXPHOS disorder, phenotypically distinct from other types of Leigh syndrome, with a carrier frequency up to 1:23 and an incidence of 1:2063 in the Saguenay-Lac-St Jean region of Quebec. Recently, LSFC has also been reported outside the French-Canadian population. Patient presentation We report a male Italian (Sicilian) child, born preterm at 28 + 6/7 weeks gestation, carrying a novel LRPPRC compound heterozygous mutation, with facial dysmorphisms, neonatal hypotonia, non-epileptic paroxysmal motor phenomena, and absent sucking-swallowing-breathing coordination requiring, at 4.5 months, a percutaneous endoscopic gastrostomy tube placement. At 5 months brain Magnetic Resonance Imaging showed diffuse cortical atrophy, hypoplasia of corpus callosum, cerebellar vermis hypoplasia, and unfolded hippocampi. Both auditory and visual evoked potentials were pathological. In the following months Video EEG confirmed the persistence of sporadic non epileptic motor phenomena. No episode of metabolic decompensation, acidosis or ketosis, frequently observed in LSFC has been reported. Actually, aged 14 months corrected age for prematurity, the child shows a severe global developmental delay. Metabolic investigations and array Comparative Genomic Hybridization (aCGH) results were normal. Whole-exome sequencing (WES) found a compound heterozygous mutation in the LRPPRC gene, c.1921–7A > G and c.2056A > G (p.Ile686Val), splicing-site and missense variants, inherited from the mother and the father, respectively. Conclusions We first characterized the clinical and molecular features of a novel LRPPRC variant in a male Sicilian child with early onset encephalopathy and psychomotor impairment. Our patient showed a phenotype characterized by a severe neurodevelopmental delay and absence of metabolic decompensation attributable to a probable residual enzymatic activity. LRPPRC is a rare cause of metabolic encephalopathy outside of Québec. Our patient adds to and broaden the spectrum of LSFC phenotypes. WES analysis is a pivotal genetic test and should be performed in infants and children with hypotonia and developmental delay in whom metabolic investigations and aCGH are normal.

show abstract

“…To our knowledge, TS14 has been identified in 58 patients, including 10 patients with epimutations of the IG-DMR and the MEG3 -DMR, and KOS14 has been identified in 57 patients, including 7 patients with epimutations of the two DMRs. 1,2,6,7,8,9 Thus, we examined MLIDs in TS14 and KOS14 caused by epimutations.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome

Kagami

Matsubara

Nakabayashi

et al. 2017

Genetics in Medicine

View full text Add to dashboard Cite

Purpose:Recent studies have identified multilocus imprinting disturbances (MLIDs) in a subset of patients with imprinting diseases (IDs) caused by epimutations. We examined MLIDs in patients with Temple syndrome (TS14) and Kagami-Ogata syndrome (KOS14).Methods:We studied four TS14 patients (patients 1–4) and five KOS14 patients (patients 5–9) with epimutations. We performed HumanMethylation450 BeadChip (HM450k) analysis for 43 differentially methylated regions (DMRs) (753 CpG sites) and pyrosequencing for 12 DMRs (62 CpG sites) using leukocyte genomic DNA (Leu-gDNA) of patients 1–9, and performed HM450k analysis for 43 DMRs (a slightly different set of 753 CpG sites) using buccal cell gDNA (Buc-gDNA) of patients 1, 3, and 4. We also performed mutation analysis for six causative and candidate genes for MLIDs and quantitative expression analysis using immortalized lymphocytes in MLID-positive patients.Results:Methylation analysis showed hypermethylated ZDBF2-DMR and ZNF597/NAA60-DMR, hypomethylated ZNF597-DMR in both Leu-gDNA and Buc-gDNA, and hypomethylated PPIEL-DMR in Buc-gDNA of patient 1, and hypermethylated GNAS-A/B-DMR in Leu-gDNA of patient 3. No mutations were detected in the six genes for MLIDs. Expression patterns of ZDBF2, ZNF597, and GNAS-A/B were consistent with the identified MLIDs.Conclusion:This study indicates the presence of MLIDs in TS14 patients but not in KOS14 patients.Genet Med 19 4, 476–482.

show abstract

Paternal uniparental disomy chromosome 14‐like syndrome due a maternal de novo 160 kb deletion at the 14q32.2 region not encompassing the IG‐ and the MEG3‐DMRs: Patient report and genotype–phenotype correlation

Cited by 17 publications

References 52 publications

Novel microdeletions on chromosome 14q32.2 suggest a potential role for non-coding RNAs in Kagami-Ogata syndrome

Novel microdeletions on chromosome 14q32.2 suggest a potential role for non-coding RNAs in Kagami-Ogata syndrome

Novel LRPPRC compound heterozygous mutation in a child with early-onset Leigh syndrome French-Canadian type: case report of an Italian patient

Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome

Contact Info

Product

Resources

About