The Benefits of Whole-Exome Sequencing in the Differential Diagnosis of Hypophosphatasia.

Autor:	Glotov, Oleg S., Zhuchenko, Natalya A., Balashova, Maria S., Raspopova, Aleksandra N., Tsai, Victoria V., Chernov, Alexandr N., Chuiko, Iana V., Danilov, Lavrentii G., Morozova, Lyudmila D., Glotov, Andrey S.
Předmět:	GENETIC variation GENETIC testing ALKALINE phosphatase RARE diseases GENETIC disorders
Zdroj:	International Journal of Molecular Sciences; Nov2024, Vol. 25 Issue 21, p11728, 25p
Abstrakt:	Hypophosphatasia (HPP) is a rare inherited disorder characterized by the decreased activity of tissue-nonspecific alkaline phosphatase (TNSALP), caused by mutations in the ALPL gene. The aim of this study was to conduct differential diagnostics in HPP patients using whole-exome sequencing (WES). The medical records of HPP patients and the genetic testing of the ALPL gene were reviewed. Seven patients were recruited and underwent WES using the Illumina or MGI sequencing platforms. All of the exome samples were matched onto a GRCh38.p13 reference genome assembly by using the Genome Analysis ToolKit (GATK) and the BWA MEM read aligner. We present the clinical and molecular findings of the seven patients referred for genetic analyses due to a clinical and biochemical suspicion of HPP. In two patients out of three (with identified heterozygous variants in the ALPL gene), we also identified c.682T>A in exon 3 of the WNT10A gene and c.3470del in exon 23 of the SMC1A gene variants for the first time. In four patients, variants in the ALPL gene were not detected, but WES allowed us to identify for the first time rare variants (c.5651A>C in exon 36 of the TRIO gene, c.880T>G in exon 6 of the TRPV4 gene, c.32078-1G>T in intron 159 of the TTN gene, c.47720_47721del in exon 235 of the TTN gene, and c.1946G>A in exon 15 of the SLC5A1 gene) and to conduct differential diagnostics with HPP. Using WES, for the first time, we demonstrate the possibility of early differential diagnostics in HPP patients with other rare genetic diseases. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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