Sylwia Purwin

X-chromosome inactivation (XCI) is an epigenetic regulatory mechanism thatequalizes the expression of X-linked genes between the sexes. Although this processis physiological, it can become disrupted, leading to phenotypic variabilityin women who are carriers of X-linked recessive mutations. This paper reviewsthe mechanisms of XCI, the factors influencing the randomness of this processand its clinical significance in women. We present literature data on the variabilityof XCI patterns across different tissues and on diseases in which non-random inactivationpattern affects the clinical manifestation in women. The diagnostic valueof the HUMARA test and its limitations in routine XCI analysis are also discussed.

Objective: Copy number variants (CNVs) overlapping genes associated with neurodevelopmental disorders in patients with epilepsy are particularly concentrated in epilepsy hotspot loci. The aim of this study was to evaluate epilepsy as a component of the dysmorphic–neurodevelopmental phenotype in patients with recurrent CNVs. Methods: The study included genetic and clinical data from 177 pediatric patients carrying 17 recurrent CNVs showing well-documented enrichment in epilepsy or associated with genetic OMIM syndromes. Results: Epilepsy was diagnosed in 50 of 177 children (28.2%), developmental delay in 147 (83.0%), dysmorphic features in 104 (58.8%), behavioral problems in 62 (35.0%), and congenital anomalies in 55 (31.1%). Among recurrent CNV hotspots, the del16p11.2 BP4–BP5 deletion was the most frequent, occurring in 39 of 177 patients. Ten children (25.6%) with del16p11.2 presented with epilepsy as part of the phenotype. Other frequently represented CNVs included del15q11.2 BP1–BP2 (OMIM #615656; 19/177 patients, 4/19 with epilepsy), del1q21.1 (OMIM #612474; 15/177, 6/15 with epilepsy), del15q13.3 (OMIM #612001; 13/177, 4/13 with epilepsy), and dup16p11.2 (OMIM #614671; 12/177, 1/12 with epilepsy). The highest proportion of epilepsy as a phenotypic component was observed in patients with del1p36 (OMIM #607872; 6/9 patients) and del1q21.1 (OMIM #612474; 6/15 patients). Conclusions: Our data support the clinical utility of CNV testing in patients with epilepsy accompanied by additional neurodevelopmental or dysmorphic features, in line with current diagnostic guidelines. The epilepsy-plus phenotype may help clinicians identify patients who are most likely to benefit from CNV analysis.

Prenatal genetic diagnosis includes screening tests (to assess the risk of chromosomal aberrations) and diagnostic tests (to identify changes in DNA). The dynamic development of molecular methods in prenatal diagnosis has significantly expanded diagnostic possibilities, and techniques based on next-generation sequencing (NGS) are playing an increasingly important role. The wider availability and scope of prenatal tests contributes to early and more precise diagnosis and helps to improve a perinatal care and clinical management after birth. This article presents genetic techniques currently used in Poland in prenatal diagnosis and related current clinical guidelines.