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Interstitial 1p deletions are rare events. Very few cases of 1p31.1p31.3 deletions characterized by variable phenotypes have been reported. No clear genotype-phenotype correlation has been determined yet. We present a child with a de novo interstitial 1p31.1p31.3 deletion, identified by array CGH, associated with intellectual disability and severe language impairment. The deleted region contains 20 OMIM genes, but we focused on GADD45A (MIM 126335; growth arrest- and DNA damage-inducible gene), LRRC7 (MIM 614453; leucine-rich repeat-containing protein 7), and NEGR1 (MIM 613173; neuronal growth regulator 1). We discuss whether these genes play a role in determining the phenotype of our patient in order to investigate the possibility of a genotype-phenotype correlation., (© 2015 S. Karger AG, Basel.)

Whole genome profiling such as array comparative genomic hybridization has identified novel genomic imbalances. Copy number studies led to an explosion of the discoveries of new segmental duplication-mediated deletions and duplications. These rearrangements are mostly the result of non-allelic homologous recombination (NAHR) between low-copy repeats or segmental duplications. We have identified an individual with a small, rare deletion on chromosome 2q21.1 with psychomotor delay, hyperactivity, and aggressive behavior. The rearranged region is flanked by large complex low-copy repeats and includes only five genes: GPR148, FAM123C (AMER3), ARHGEF4, FAM168B, and PLEKHB2. The comparison between our patient and the cases previously reported in the literature contributes to a better definition of genotype-phenotype correlation of 2q21.1 microdeletions., (© 2013 Wiley Periodicals, Inc.)

Mutations in neuronal voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A may play an important role in the etiology of neurological diseases and psychiatric disorders, besides various types of epilepsy. Here we describe a 3-year-old boy with autistic features, language delay, microcephaly and no history of seizures. Array-CGH analysis revealed an interstitial deletion of ~291.9kB at band 2q24.3 disrupting the entire SCN2A gene and part of SCN3A. We discuss the effects of haploinsufficiency of SCN2A and SCN3A on the genetic basis of neurodevelopmental and neurobehavioral disorders and we propose that this haploinsufficiency may be associated not only with epilepsy, but also with autistic features., (© 2013 Elsevier B.V. All rights reserved.)

Background: terminal deletions of the distal portion of the short arm of chromosome 3 cause a rare contiguous gene disorder characterized by growth retardation, developmental delay, mental retardation, dysmorphisms, microcephaly and ptosis. The phenotype of individuals with deletions varies from normal to severe. It was suggested that a 1,5 Mb minimal terminal deletion including the two genes CRBN and CNTN4 is sufficient to cause the syndrome. In addition the CHL1 gene, mapping at 3p26.3 distally to CRBN and CNTN4, was proposed as candidate gene for a non specific mental retardation because of its high level of expression in the brain., Methods and Results: we describe two affected siblings in which array-CGH analysis disclosed an identical discontinuous terminal 3p26.3 deletion spanning less than 1 Mb. The deletion was transmitted from their normal father and included only the CHL1 gene. The two brothers present microcephaly, light mental retardation, learning and language difficulties but not the typical phenotype manifestations described in 3p- syndrome., Conclusion: a terminal 3p26.3 deletion including only the CHL1 gene is a very rare finding previously reported only in one family. The phenotype of the affected individuals in the two families is very similar and the deletion has been inherited from an apparently normal parent. As already described for others recurrent syndromes with variable phenotype, these findings are challenging in genetic counselling because of an evident variable penetrance.