STS and PUDP Deletion Identified by Targeted Panel Sequencing with CNV Analysis in X-Linked Ichthyosis: A Case Report and Literature Review

Abstract

X-linked recessive ichthyosis (XLI) is clinically characterized by dark brown, widespread dryness with polygonal scales. We describe the identification of STS and PUDP deletions using targeted panel sequencing combined with copy-number variation (CNV) analysis in XLI. A 9-month-old infant was admitted for genetic counseling. Since the second day after birth, the infant’s skin tended to be dry and polygonal scales had accumulated over the abdomen and upper extremities. The infant’s maternal uncle and brother (who had also exhibited similar skin symptoms from birth) presented with polygonal scales on their trunks. CNV analysis revealed a hemizygous deletion spanning 719.3 Kb on chromosome Xp22 (chrX:7,108,996–7,828,312), which included a segment of the STS gene and exhibited a Z ratio of −2 in the proband. Multiplex ligation-dependent probe amplification (MLPA) confirmed this interstitial Xp22.31 deletion. Our report underscores the importance of implementing CNV screening techniques, including sequencing data analysis and gene dosage assays such as MLPA, to detect substantial deletions that encompass the STS gene region of Xq22 in individuals suspected of having XLI.

Comprehensive Molecular Analysis of Disease-Related Genes as First-Tier Test for Early Diagnosis, Classification, and Management of Patients Affected by Nonsyndromic Ichthyosis

“…The high success rate of our methodology was mostly due to a data analysis strategy that, in addition to known and new disease-causing SNVs, was able to reveal heterozygous and hemizygous large deletions, therefore confirming elevated sensitivity also for the detection of these types of CNV [17]. Indeed, as very recently reported [27], accessibility to raw sequence data and manual review of suspicious sequence regions allows for reducing false-negative results in the clinical application of NGS. Considering, however, the limited sample size and issues such as insufficient coverage depth of a few target regions, our results do not provide sufficient basis for a broad conclusion regarding the real efficacy of this genetic testing approach.…”