ABSTRACT
Epidermolysis bullosa (EB) is a rare and genetically heterogeneous disorder characterized by skin fragility and blister formation occurring spontaneously or after minor trauma. EB is accompanied by congenital absence of skin (EB with CAS) in some patients. Pathogenic variants of COL7A1 are responsible for EB with CAS in the vast majority of cases. Type and subtype diagnosis of EB with CAS generally requires specific immunohistological examinations that are not widely available plus targeted gene analysis. The present study aimed to determine the clinical features of five patients affected by EB with CAS and to identify the underlying genetic defects using whole exome sequencing (WES) followed by focused analysis of the target genes. Four patients had generalized skin involvement and one had localized defects. Two patients exhibited extremely severe skin manifestations and congenital cloudy cornea along with pyloric atresia, and one had partial esophagogastric obstruction and anuria due to vesicoureteric obstruction. In the WES analysis, the average coverage of the target exons was 99.05% (726 of 733 exons), with a range of 96.4-100% for individual genes. We identified four novel and two known pathogenic/likely pathogenic variants of five distinct genes in the examined families: PLEC:c.2536G > T (p.Glu846Ter); LAMC2:c.3385C > T (p.Arg1129Ter); KRT5:c.429G > A (p.Glu477Lys); ITGB4:c.794dupC (p.Ala266SerfsTer5); COL7A1:c.5440C > T (p.Arg1814Cys); and COL7A1:c.6103delG. All alleles were inherited from the parents, except for the KRT5 variant as a de novo finding. The findings reveal extremely rare phenotypes found in EB with CAS, namely congenital cloudy cornea, esophagogastric obstruction, and anuria, and extend the genotypic spectrum of EB-related genes. The data confirm that WES provides very high coverage of coding exons/genes and support its use as a reasonable alternative method for diagnosis of EB. The present data from an underrepresented population in Southeast Asia could further broaden the knowledge and research on EB.
ABSTRACT
Background: Siblings of children with autism spectrum disorders (ASD) have higher prevalence of ASD with a recurrence of 19%. Children with ASD demonstrate significant impairment in all types of imitative skills. Imitation is markedly developed in the first few years of life; therefore, a study of imitation in younger siblings in this period may reveal early deviation. Objective: To study the development of imitation skills from 9- to 18-months, specifying types of imitation, in siblings of children with ASD compared with typically developing children. Method and Material: A longitudinal case-control study was conducted on eight siblings of children with ASDs and nineteen typically developing children who were age- and gender-matched. Data collection consisted of parental recording of emerging imitative abilities and structured direct observation of imitative skills at 9, 12 and 18 months. Three types of imitative skills were targeted including vocal, object and gesture imitation. Results: The development of vocal imitation in siblings of children with ASD between 12 to 18 months was delayed in comparison with typically developing children with significant statistical difference at 18 months. Object and gesture imitations were not significantly different between the two groups. Conclusion: Siblings of children with ASDs had some delays in vocal imitation skills at the age of 12 to 18 months, compared with typically developing children.
