SLC26A2/DTDST Spectrum: A Cohort of 12 Patients Associated with a Comprehensive Review of the Genotype-Phenotype Correlation

Molecular syndromology

article

Silveira, Cynthia¹  da Costa Silveira, Karina¹  Lacarrubba-Flores, Maria D.¹  Sakata, Maurício T.¹  Carbognani, Silvia N.²  Llerena Jr., Juan³  Moreno, Carolina A.⁵  Cavalcanti, Denise P.¹ 

[1] Skeletal Dysplasia Group, Department of Translational Medicine, Faculty of Medical Sciences, University of Campinas;Maternidad Oroño;Centro de Genética Médica &Centro de Referência para Doenças Raras;Perinatal Genetic Program, Department of Translational Medicine, University of Campinas

关键词: SLC26A2/DTDST;    Diastrophic dysplasia;    rMED;    AO2;    ACG1B;    Swedish key proximal femur;   

DOI  :  10.1159/000525020

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

Introduction: Pathogenic variants in the SLC26A2/DTDST gene cause the following spectrum of phenotypes: achondrogenesis 1B (ACG1B), atelosteogenesis 2 (AO2), diastrophic dysplasia (DTD), and recessive-multiple epiphyseal dysplasia (rMED), the first 2 being lethal. Here, we report a cohort and a comprehensive literature review on a genotype-phenotype correlation of SLC26A2/DTDST-related disorders. Methods: The local patients were genotyped by Sanger sequencing or next-generation sequencing (NGS). We reviewed data from the literature regarding phenotype, zygosity, and genotype in parallel. Results: The local cohort enrolled 12 patients, including one with a Desbuquois-like phenotype. All but one showed biallelic mutations, however, only one allele mutated in a fetus presenting ACG1B was identified. The literature review identified 42 articles and the analyses of genotype and zygosity included the 12 local patients. Discussion:C, R178*, K575Sfs*10, V340del, G663R, T512K). The last 3 in hmz lead to lethal phenotypes. The Finnish mutation is found only in chtz outside of Finland, being associated with all 4 classical phenotypes. The p.R178* and p.K575Sfs*10 variants should be viewed as lethal mutations since both were mainly described with lethal phenotypes and were never reported in hmz. The existence of 9 patients with only one mutated allele suggests that other mutations in the other allele of these patients still need to be unveiled.

【 授权许可】

CC BY