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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

Face of the proband at age of 2 years and 3 months showing mild facial dysmorphic features listed in the text
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Fig1: Face of the proband at age of 2 years and 3 months showing mild facial dysmorphic features listed in the text

Mentions: Medical Geneticist first clinically assessed the patient at 2 years and 3 months. His height was 96 cm (90–97th centile), weight was 15 kg (75–90th centile) and head circumference was 52 cm (50–75th centile). Physical examination revealed minor dysmorphic facial features consisting of mild hypertelorism, down-slanting long palpebral fissures with eversion of lateral third of lower eyelids, long philtrum, thin upper lip, mildly prominent ear lobes (Fig. 1). Sleeping and feeding have been considered normal, as well as brain MRI, EEG, ECG, ocular and audiological assessment, abdomen echography, carpal bone X-rays. Routine blood exams, aminoacidemia/aminoaciduria, urinary organic acids’ panel and acyl-carnitine blood spot were all in normal ranges.Fig. 1


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)

Face of the proband at age of 2 years and 3 months showing mild facial dysmorphic features listed in the text
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Face of the proband at age of 2 years and 3 months showing mild facial dysmorphic features listed in the text
Mentions: Medical Geneticist first clinically assessed the patient at 2 years and 3 months. His height was 96 cm (90–97th centile), weight was 15 kg (75–90th centile) and head circumference was 52 cm (50–75th centile). Physical examination revealed minor dysmorphic facial features consisting of mild hypertelorism, down-slanting long palpebral fissures with eversion of lateral third of lower eyelids, long philtrum, thin upper lip, mildly prominent ear lobes (Fig. 1). Sleeping and feeding have been considered normal, as well as brain MRI, EEG, ECG, ocular and audiological assessment, abdomen echography, carpal bone X-rays. Routine blood exams, aminoacidemia/aminoaciduria, urinary organic acids’ panel and acyl-carnitine blood spot were all in normal ranges.Fig. 1

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