Spread of X-chromosome inactivation into autosomal regions in patients with unbalanced X-autosome translocations and its phenotypic effects.

Patients with unbalanced X-autosome translocations are rare and usually present a skewed X-chromosome inactivation (XCI) pattern, with the derivative chromosome being preferentially inactivated, and with a possible spread of XCI into the autosomal regions attached to it, which can inactivate autosomal genes and affect the patients' phenotype. We describe three patients carrying different unbalanced X-autosome translocations, confirmed by G-banding karyotype and array techniques. We analyzed their XCI pattern and inactivation spread into autosomal regions, through HUMARA, ZDHHC15 gene assay and the novel 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, and identified an extremely skewed XCI pattern toward the derivative chromosomes for all the patients, and a variable pattern of late-replication on the autosomal regions of the derivative chromosomes.

Williams-Beuren syndrome in diverse populations.

Williams-Beuren syndrome (WBS) is a common microdeletion syndrome characterized by a 1.5Mb deletion in 7q11.23.

Autism spectrum disorder in a girl with a de novo x;19 balanced translocation.

Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with a de novo X;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects.

Detection of classical 17p11.2 deletions, an atypical deletion and RAI1 alterations in patients with features suggestive of Smith-Magenis syndrome.

Smith-Magenis syndrome (SMS) is a complex disorder whose clinical features include mild to severe intellectual disability with speech delay, growth failure, brachycephaly, flat midface, short broad hands, and behavioral problems. SMS is typically caused by a large deletion on 17p11.2 that encompasses multiple genes including the retinoic acid induced 1, RAI1, gene or a mutation in the RAI1 gene.