A Case of CDKL5 Deficiency Due to an X Chromosome Pericentric Inversion: Delineation of Structural Rearrangements as an Overlooked Recurrent Pathological Mechanism.

CDKL5 deficiency disorder (CDD) is an X-linked dominant epileptic encephalopathy, characterized by early-onset and drug-resistant seizures, psychomotor delay, and slight facial features. Genomic variants inactivating or impairing its protein product kinase activity have been reported, making next-generation sequencing (NGS) and chromosomal microarray analysis (CMA) the standard diagnostic tests. We report a suspicious case of CDD in a female child who tested negative upon NGS and CMA and harbored an X chromosome de novo pericentric inversion.

Hypoplastic left heart syndrome and 21q22.3 deletion.

Hypoplastic left heart syndrome (HLHS) is a rare congenital heart defect (CHD), associated with extracardiac anomalies in the 15-28% of cases, in the setting of chromosomal anomalies, mendelian disorders, and organ defects. We report on a syndromic female newborn with HLHS and terminal 21q22.3 deletion (del 21q22.

Endocrine autoimmunity in Turner syndrome.

Background: Turner syndrome is caused by numeric and structural abnormalities of the X chromosome. An increased frequency of autoimmunity as well as an elevated incidence of autoantibodies was observed in Turner patients. The aim of this study was to conduct a retrospective analysis of the incidence of autoimmunity in 66 Italian patients affected by Turner syndrome.

Array-CGH characterization and genotype-phenotype analysis in a patient with a ring chromosome 6.

Background: Ring chromosome 6 is a rare constitutional abnormality that generally occurs de novo. The related phenotype may be highly variable ranging from an almost normal phenotype to severe malformations and mental retardation. These features are mainly present when genetic material at the end of the chromosome is lost.

Characterization of a novel isolated deletion of the exon 3 within the CFTR gene: Relevance for phenotypic expression and genetic counseling.

Objectives: To characterize a novel deletion of exon 3 of CFTR gene and to evaluate the implications in Cystic Fibrosis (CF) care and genetic counseling.

Design And Methods: We performed a wide mutational analysis of CFTR gene, using reverse dot blot, Multiplex Ligation-dependent Probe Amplification (MLPA) assay and Real Time Quantitative PCR, in a carrier male and two CF patients with the F508del mutation.

Results: We found a novel isolate 538bp deletion of exon 3, described as 328del538, giving rise to a nonsense codon 60bp at the 3' end of the new coding sequence or, alternatively, a novel splice site at the breakpoints.

Complex chromosome rearrangements related 15q14 microdeletion plays a relevant role in phenotype expression and delineates a novel recurrent syndrome.

Complex chromosome rearrangements are constitutional structural rearrangements involving three or more chromosomes or having more than two breakpoints. These are rarely seen in the general population but their frequency should be much higher due to balanced states with no phenotypic presentation. These abnormalities preferentially occur de novo during spermatogenesis and are transmitted in families through oogenesis.

Lyonization effects of the t(X;16) translocation on the phenotypic expression in a rare female with Menkes disease.

Menkes disease (MD) is a rare and severe X-linked recessive disorder of copper metabolism. The MD gene, ATP7A (ATPase Cu++ transporting alpha polypeptide), encodes an ATP-dependent copper-binding membrane protein. In this report, we describe a girl with typical clinical features of MD, carrying a balanced translocation between the chromosomes X and 16 producing the disruption of one copy of ATP7A gene and the silencing of the other copy because of the chromosome X inactivation.