Report on 3 patients with 12p duplication including GRIN2B

Poirsier, Céline; Landais, Emilie; Bednarek, Nathalie; Nobecourt, Jean-Marie; Khoury, Maroun; Schmidt, Pascal; Morville, Patrice; Gruson, Nadine; Clomes, Sandrine; Michel, Nicole; Riot, Anita; Manjeongean, Christelle; Gaillard, Dominique; Doco‐Fenzy, Martine

doi:10.1016/j.ejmg.2013.12.009

Cited by 5 publications

(8 citation statements)

References 26 publications

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“…8; 12). In addition, our patient showed common facial features with cases of pure and complete 12p duplication, such as a round face, short nose, thin upper lip, and short neck, which is in agreement with previous studies showing that the facial features of trisomy 12p syndrome are linked to genes at the distal 12p region [Segel et al, 2006;Izumi et al, 2012;Poirsier et al, 2014]. Our patient also manifested increased birth weight and neonatal complications such as hypotonia, poor feeding, and hypoglycemia resembling those of trisomy 12p.…”

Section: Discussionsupporting

confidence: 91%

“…Several patients also displayed accelerated growth, brain MRI abnormalities and respiratory difficulties. Interestingly, many of these features are frequently seen in 12p duplication, such as DD, hypotonia, seizures, 'social' behavior, macrocephaly, and some of the facial features [Segel et al, 2006;Izumi et al, 2012;Poirsier et al, 2014], suggesting the presence of genes on 12p responsible for various aspects of t(8; 12) phenotype.…”

Section: Discussionmentioning

confidence: 99%

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Two New Cases of 1p21.3 Deletions and an Unbalanced Translocation t(8;12) among Individuals with Syndromic Obesity

et al. 2015

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due to duplication of the GNB3 gene. Thus, our findings add to the existing literature on the clinical description of these new syndromes, providing additional support that these loci are associated with syndromic obesity. We suggest that heterozygous loss of MIR137 may contribute to obesity as well as ID and ASD. AbstractObesity is a highly heritable but genetically heterogeneous disorder. Various well-known microdeletion syndromes (e.g. 1p36, 2q37, 6q16, 9q34, 17p11.2) can cause this phenotype along with intellectual disability (ID) and other findings. Chromosomal microarrays have identified 'new' microdeletion/duplication syndromes often associated with obesity. We report on 2 unrelated patients with an overlapping region of deletion at 1p21.3p21.2, and a third patient with a de novo recurrent unbalanced translocation der(8)t(8; 12) (p23.1;p13.31), detected by 180K array CGH in a prospective cohort of syndromic obesity patients. Deletion of 1p21.3 is a rare condition, and there have been only 11 cases of the same recurrent translocation between chromosomes 8 and 12 [t(8; 12)] reported to date. The former has been associated with ID, autistic spectrum disorder (ASD) and mild dysmorphic features, and in 4 patients who were obese or had a tendency to obesity, a minimal overlapping region of 2 genes, DPYD and MIR137 , was detected; t(8; 12) has recently been recognized to cause a childhood obesity syndrome

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Two New Cases of 1p21.3 Deletions and an Unbalanced Translocation t(8;12) among Individuals with Syndromic Obesity

et al. 2015

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“…This same translocation was identified in 3 similarly affected relatives (7). Further, a microdeletion encompassing the GRIN2A gene (16p13.2p13.13) was identified in three patients with variable mild to severe intellectual disability and seizures (8) and overlapping duplications of chromosome 12p points towards GRIN2B in a series of patients with a variable DD and ID phenotype (31). Thus, a comparative analysis of GRIN translocations and microdeletions could be informative.…”

Section: Grin2b Mutations With Chromosome Translocationmentioning

confidence: 99%

Human GRIN2B variants in neurodevelopmental disorders

Chen

Myers

et al. 2016

Journal of Pharmacological Sciences

191

156

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The development of whole exome/genome sequencing technologies has given rise to an unprecedented volume of data linking patient genomic variability to brain disorder phenotypes. A surprising number of variants have been found in the N-methyl-D-aspartate receptor (NMDAR) gene family, with the GRIN2B gene encoding the GluN2B subunit being implicated in many cases of neurodevelopmental disorders, which are psychiatric conditions originating in childhood and include language, motor, and learning disorders, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), developmental delay, epilepsy, and schizophrenia. The GRIN2B gene plays a crucial role in normal neuronal development and is important for learning and memory. Mutations in human GRIN2B were distributed throughout the entire gene in a number of patients with various neuropsychiatric and developmental disorders. Studies that provide functional analysis of variants are still lacking, however current analysis of de novo variants that segregate with disease cases such as intellectual disability, developmental delay, ASD or epileptic encephalopathies reveal altered NMDAR function. Here, we summarize the current reports of disease-associated variants in GRIN2B from patients with multiple neurodevelopmental disorders, and discuss implications, highlighting the importance of functional analysis and precision medicine therapies.

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“…Compared with cases described in the literature with "pure" partial duplication 12p similar to the duplication region of our patient, the clinical description included a round face, full checks, proeminent forehead/frontal, short nose, wide/depressed nasal bridge, anteverted nostril, long/deep philtrum, large downward facing mouth, and inverted lower lip (Table 1) are present in most cases of Category I and subgroup D (De Gregori et al, 2005;Liang et al, 2006;Poirsier et al, 2014).…”

mentioning

confidence: 69%

“…Approximately 50 cases of duplications 12p have been described in the medical literature to date consisting of small studies and case reports, that are limited to descriptions of the clinical syndrome at birth or in early infancy. Little is known about the life expectancy of these children, beyond infancy and most of the diagnostic criteria are based on descriptions of infants and adolescents (Segel et al, 2006;Inage et al, 2010;Liu et al, 2012;Poirsier et al, 2014;Mekkawy et al, 2016). The clinical signs most com-monly associated with duplication 12p are increased weight at birth, hypotonia, craniofacial anomalies such as turricephaly, macrocephaly, round face, full cheeks, frontal bossing, wide nasal bridge, short nose, anteverted nares, long philtrum, thin upper lip, short neck, dysmorphic ears, intellectual impairment and moderate to severe psychomotor delay (Hung et al, 2012;Poirsier et al, 2014).…”

mentioning

confidence: 99%

Non-mosaic partial duplication 12p in a patient with dysmorphic characteristics and developmental delay

et al. 2020

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Duplication of the short arm of chromosome 12 is a rare chromosomal abnormality that may arise de novo or result from malsegregation of a balanced parental translocation. This study comprises the clinical description, cytogenetic and cytogenomic analyses and genotype-phenotype correlation in a patient with facial dysmorphism, developmental delay and intellectual impairment caused by non-mosaic partial duplication and a paracentric inversion 12p. The patient's GTG-banded karyotype was 46,XX,invdup(12)(pter ® p13.32::p11.1 ® p13.31::p13.31 ® qter). A genetic gain of approximately 28 Mb was detected in the chromosomal region arr[GRCh37]12p13.31-p11.1(6914072_34756209)x3. The chromosomal alteration seen in our patient is described as "pure" partial duplication 12p. In most cases, duplication 12p phenotype is characterized by dysmorphic features, multiple congenital anomalies and intellectual disability. A small number of cases in literature have described genes associated with neurodevelopmental disease, such as ING4, CHD4, MFAP5, GRIN2B, SOX5, SCN8A and PIANP. In our patient the duplication 12p was de novo. This study should contribute to the genotype-phenotype correlation in partial duplication 12p cases.

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Report on 3 patients with 12p duplication including GRIN2B

Cited by 5 publications

References 26 publications

Two New Cases of 1p21.3 Deletions and an Unbalanced Translocation t(8;12) among Individuals with Syndromic Obesity

Two New Cases of 1p21.3 Deletions and an Unbalanced Translocation t(8;12) among Individuals with Syndromic Obesity

Human GRIN2B variants in neurodevelopmental disorders

Non-mosaic partial duplication 12p in a patient with dysmorphic characteristics and developmental delay

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