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

被引:0
作者
Glotov, Oleg S. [1 ,2 ,3 ]
Zhuchenko, Natalya A. [4 ]
Balashova, Maria S. [1 ,4 ]
Raspopova, Aleksandra N. [3 ]
Tsai, Victoria V. [1 ,2 ,3 ]
Chernov, Alexandr N. [1 ,5 ,6 ]
Chuiko, Iana V. [7 ]
Danilov, Lavrentii G. [3 ,8 ]
Morozova, Lyudmila D. [4 ]
Glotov, Andrey S. [1 ,8 ]
机构
[1] DO Ott Res Inst Obstet Gynecol & Reproductol, Dept Genom Med, St Petersburg 199034, Russia
[2] Mol Genet & Biobanking Pediat Res & Clin Ctr Infec, Dept Expt Med Virol, St Petersburg 197022, Russia
[3] CerbaLab Ltd, St Petersburg 199106, Russia
[4] IM Sechenov First Moscow State Med Univ, Dept Med Genet, NV Sklifosovsky ICM, Moscow 119991, Russia
[5] Inst Expt Med, Dept Gen Pathol & Pathol Physiol, St Petersburg 197022, Russia
[6] St Petersburg State Pediat Med Univ, Fed State Budgetary Educ Inst Higher Educ, Minist Hlth Russia, Dept Biol Chem, St Petersburg 194100, Russia
[7] Moscow State Univ, Fac Bioengn & Bioinformat, Moscow 119991, Russia
[8] St Petersburg State Univ, Dept Genet & Biotechnol, St Petersburg 199034, Russia
关键词
hypophosphatasemia; whole-exome sequencing; differential diagnosis; phenotypic overlaps; rare diseases; ALPL gene pathogenic variants; clinical cases; ALKALINE-PHOSPHATASE; VARIANTS; CHILDREN; ZINC; ALPL;
D O I
10.3390/ijms252111728
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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共 56 条
[1]   Congenital Glucose-Galactose Malabsorption: A Case With a Novel SLC5A1 Mutation in a Saudi Infant [J].
Alamoudi, Loujen O. ;
Alfaraidi, Albaraa T. ;
Althagafi, Samiyah S. ;
Al-Thaqafy, Majid S. ;
Hasosah, Mohammed .
CUREUS JOURNAL OF MEDICAL SCIENCE, 2021, 13 (10)
[2]  
alplmutationdatabase.hypophosphatasie.com, ALPL Mutation Database
[3]  
Auton A., 2015, The 1000 Genomes Project, P71
[4]  
[Баранов А.А. Baranov Alexander A.], 2016, [Педиатрическая фармакология, Pediatric pharmacology, Pediatricheskaya farmakologiya], V13, P539, DOI 10.15690/pf.v13i6.1665
[5]   Whole-exome sequencing provides insights into monogenic disease prevalence in Northwest Russia [J].
Barbitoff, Yury A. ;
Skitchenko, Rostislav K. ;
Poleshchuk, Olga, I ;
Shikov, Anton E. ;
Serebryakova, Elena A. ;
Nasykhova, Yulia A. ;
Polev, Dmitrii E. ;
Shuvalova, Anna R. ;
Shcherbakova, Irina, V ;
Fedyakov, Mikhail A. ;
Glotov, Oleg S. ;
Glotov, Andrey S. ;
Predeus, Alexander, V .
MOLECULAR GENETICS & GENOMIC MEDICINE, 2019, 7 (11)
[6]   The diagnosis of hypophosphatasia in children as a multidisciplinary effort: an expert opinion [J].
Baroncelli, G. I. ;
Carlucci, G. ;
Freri, E. ;
Giuca, M. R. ;
Guarnieri, V. ;
Navarra, G. ;
Toschi, B. ;
Mora, S. .
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, 2024, 47 (03) :739-747
[7]   Hypophosphatasia and cleidocranial dysplasia-a case report and review of the literature: the role of the neurosurgeon [J].
Blionas, Alexandros ;
Friehs, Gerhard M. ;
Zerris, Vasileios A. .
CHILDS NERVOUS SYSTEM, 2022, 38 (02) :461-464
[8]   Clinical and molecular description of the first Italian cohort of 33 subjects with hypophosphatasia [J].
Cinque, Luigia ;
Pugliese, Flavia ;
Salcuni, Antonio Stefano ;
Trombetta, Domenico ;
Battista, Claudia ;
Biagini, Tommaso ;
Augello, Bartolomeo ;
Nardella, Grazia ;
Conti, Francesco ;
Corbetta, Sabrina ;
Fischetto, Rita ;
Foiadelli, Thomas ;
Gaudio, Agostino ;
Giannini, Cosimo ;
Grosso, Enrico ;
Guabello, Gregorio ;
Massuras, Stefania ;
Palermo, Andrea ;
Politano, Luisa ;
Pigliaru, Francesca ;
Ruggeri, Rosaria Maddalena ;
Scarano, Emanuela ;
Vicchio, Piera ;
Cannavo, Salvatore ;
Celli, Mauro ;
Petrizzelli, Francesco ;
Mastroianno, Mario ;
Castori, Marco ;
Scillitani, Alfredo ;
Guarnieri, Vito .
FRONTIERS IN ENDOCRINOLOGY, 2023, 14
[9]   The Global ALPL gene variant classification project: Dedicated to deciphering variants [J].
Farman, Mariam R. ;
Rehder, Catherine ;
Malli, Theodora ;
Rockman-Greenberg, Cheryl ;
Dahir, Kathryn ;
Martos-Moreno, Gabriel Angel ;
Linglart, Agnes ;
Ozono, Keiichi ;
Seefried, Lothar ;
del Angel, Guillermo ;
Webersinke, Gerald ;
Barbazza, Francesca ;
John, Lisa K. ;
Mudiyanselage, Sewmi M. A. Delana ;
Hoegler, Florian ;
Nading, Erica Burner ;
Huggins, Erin ;
Rush, Eric T. ;
El-Gazzar, Ahmed ;
Kishnani, Priya S. ;
Hoegler, Wolfgang .
BONE, 2024, 178
[10]   Combination of osteogenesis imperfecta and hypophosphatasia in three children with multiple fractures, low bone mass and severe osteomalacia, a challenge for therapeutic management [J].
Fratzl-Zelman, Nadja ;
Linglart, Agnes ;
Bin, Kim ;
Rauch, Frank ;
Blouin, Stephane ;
Coutant, Regis ;
Donzeau, Aurelie .
EUROPEAN JOURNAL OF MEDICAL GENETICS, 2023, 66 (11)