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De novo microduplication of CHL1 in a patient with non-syndromic developmental phenotypes.

Palumbo O, Fischetto R, Palumbo P, Nicastro F, Papadia F, Zelante L, Carella M - Mol Cytogenet (2015)

Bottom Line: Less is known about the potential effect of CHL1 overexpression, and microduplications of CHL1 have been rarely identified.To the best of our knowledge, duplication of chromosome 3p26.3, including only the CHL1 gene, has been described in only one intellectually disabled girl with epilepsy.The clinical and molecular findings reported here are useful to provide further evidence that CHL1 is a dosage sensitive gene suggesting that not only the deletion but also its duplication can cause non-syndromic neurodevelopmental phenotypes.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio di Genetica Medica, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, (FG) Italy.

ABSTRACT

Background: The CHL1 gene codes for a member of the L1 family of neural cell adhesion molecules. It is highly expressed in the central and peripheral nervous system playing an important role in the building and functioning on the brain. CHL1 proteins are also involved in axonal migration, synaptic formation and plasticity. In mice, functional studies showed that the haploinsufficiency of Chl1 gene in the developing brain results in cognitive deficits suggesting that the CHL1 gene at 3p26.3 is a candidate for an autosomal form of intellectual disability. Furthermore, in humans deletions of CHL1 have been described in patients with neurodevelopmental delay characterized by learning and language difficulties, seizures. Less is known about the potential effect of CHL1 overexpression, and microduplications of CHL1 have been rarely identified.

Case presentation: In this report, we describe a male patient with a phenotype characterized by developmental delay, symptoms of hyperactivity, short attention span and speech delay. In addition, minor facial dysmorphic features have been observed. Chromosomal microarray analysis revealed a rare de novo 0.85 Mb microduplication on the short arm (p26.3) of chromosome 3, encompassing a single gene, CHL1. To the best of our knowledge, duplication of chromosome 3p26.3, including only the CHL1 gene, has been described in only one intellectually disabled girl with epilepsy. The duplication described here is the smallest reported so far. In addition, this is the first report describing a patient in which the CHL1 duplication is a de novo event.

Conclusions: The clinical and molecular findings reported here are useful to provide further evidence that CHL1 is a dosage sensitive gene suggesting that not only the deletion but also its duplication can cause non-syndromic neurodevelopmental phenotypes.

No MeSH data available.


Related in: MedlinePlus

Chromosome microarray analysis performed with the Affymetrix CytoScan HD array and visualized using the Affymetrix Chromosome Analysis Suite version 3.0. Copy number state of each probe is drawn along chromosome 3 from 1 to 6.800.000 bp. The upper panel represents the copy number state of the proband, the middle panel the mother and the lower panel the father. Values of Y-axis indicate the inferred copy number according to probe intensities. Blue bar is the duplicated region identified in the patient
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Fig2: Chromosome microarray analysis performed with the Affymetrix CytoScan HD array and visualized using the Affymetrix Chromosome Analysis Suite version 3.0. Copy number state of each probe is drawn along chromosome 3 from 1 to 6.800.000 bp. The upper panel represents the copy number state of the proband, the middle panel the mother and the lower panel the father. Values of Y-axis indicate the inferred copy number according to probe intensities. Blue bar is the duplicated region identified in the patient

Mentions: Chromosomal microarray analysis (CMA), performed by high resolution SNP-array, showed an approximately 850 kb duplication on the short arm of chromosome 3 spanning 1,005 probes: arr[hg19]3p26.3(125,931–975,649)x3, encompassing a single coding gene, CHL1. The adjacent probes of normal copy number are at position 125,742 distally, and 978,510 proximally, for a maximum duplication size of 852 kb. The duplication was not found in the parents and was thus de novo (Fig. 2). We carefully evaluated the microarray results and we excluded the presence of other significant genomic imbalance. The duplication was confirmed by an independent array (data not showed).Fig. 2


De novo microduplication of CHL1 in a patient with non-syndromic developmental phenotypes.

Palumbo O, Fischetto R, Palumbo P, Nicastro F, Papadia F, Zelante L, Carella M - Mol Cytogenet (2015)

Chromosome microarray analysis performed with the Affymetrix CytoScan HD array and visualized using the Affymetrix Chromosome Analysis Suite version 3.0. Copy number state of each probe is drawn along chromosome 3 from 1 to 6.800.000 bp. The upper panel represents the copy number state of the proband, the middle panel the mother and the lower panel the father. Values of Y-axis indicate the inferred copy number according to probe intensities. Blue bar is the duplicated region identified in the patient
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4537544&req=5

Fig2: Chromosome microarray analysis performed with the Affymetrix CytoScan HD array and visualized using the Affymetrix Chromosome Analysis Suite version 3.0. Copy number state of each probe is drawn along chromosome 3 from 1 to 6.800.000 bp. The upper panel represents the copy number state of the proband, the middle panel the mother and the lower panel the father. Values of Y-axis indicate the inferred copy number according to probe intensities. Blue bar is the duplicated region identified in the patient
Mentions: Chromosomal microarray analysis (CMA), performed by high resolution SNP-array, showed an approximately 850 kb duplication on the short arm of chromosome 3 spanning 1,005 probes: arr[hg19]3p26.3(125,931–975,649)x3, encompassing a single coding gene, CHL1. The adjacent probes of normal copy number are at position 125,742 distally, and 978,510 proximally, for a maximum duplication size of 852 kb. The duplication was not found in the parents and was thus de novo (Fig. 2). We carefully evaluated the microarray results and we excluded the presence of other significant genomic imbalance. The duplication was confirmed by an independent array (data not showed).Fig. 2

Bottom Line: Less is known about the potential effect of CHL1 overexpression, and microduplications of CHL1 have been rarely identified.To the best of our knowledge, duplication of chromosome 3p26.3, including only the CHL1 gene, has been described in only one intellectually disabled girl with epilepsy.The clinical and molecular findings reported here are useful to provide further evidence that CHL1 is a dosage sensitive gene suggesting that not only the deletion but also its duplication can cause non-syndromic neurodevelopmental phenotypes.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio di Genetica Medica, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, (FG) Italy.

ABSTRACT

Background: The CHL1 gene codes for a member of the L1 family of neural cell adhesion molecules. It is highly expressed in the central and peripheral nervous system playing an important role in the building and functioning on the brain. CHL1 proteins are also involved in axonal migration, synaptic formation and plasticity. In mice, functional studies showed that the haploinsufficiency of Chl1 gene in the developing brain results in cognitive deficits suggesting that the CHL1 gene at 3p26.3 is a candidate for an autosomal form of intellectual disability. Furthermore, in humans deletions of CHL1 have been described in patients with neurodevelopmental delay characterized by learning and language difficulties, seizures. Less is known about the potential effect of CHL1 overexpression, and microduplications of CHL1 have been rarely identified.

Case presentation: In this report, we describe a male patient with a phenotype characterized by developmental delay, symptoms of hyperactivity, short attention span and speech delay. In addition, minor facial dysmorphic features have been observed. Chromosomal microarray analysis revealed a rare de novo 0.85 Mb microduplication on the short arm (p26.3) of chromosome 3, encompassing a single gene, CHL1. To the best of our knowledge, duplication of chromosome 3p26.3, including only the CHL1 gene, has been described in only one intellectually disabled girl with epilepsy. The duplication described here is the smallest reported so far. In addition, this is the first report describing a patient in which the CHL1 duplication is a de novo event.

Conclusions: The clinical and molecular findings reported here are useful to provide further evidence that CHL1 is a dosage sensitive gene suggesting that not only the deletion but also its duplication can cause non-syndromic neurodevelopmental phenotypes.

No MeSH data available.


Related in: MedlinePlus