| Full text | |
| Author(s): |
Silveira, Cynthia
;
Silveira, Karina da Costa
;
Lacarrubba-Flores, Maria D.
;
Sakata, Mauricio T.
;
Carbognani, Silvia N.
;
Llerena Jr, Juan
;
Moreno, Carolina A.
;
Cavalcanti, Denise P.
Total Authors: 8
|
| Document type: | Journal article |
| Source: | MOLECULAR SYNDROMOLOGY; v. N/A, p. 11-pg., 2022-06-15. |
| Abstract | |
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: The R279W variant was the most prevalent among the local patients. It was in homozygosity (hmz) in 2 patients with rMED and in compound heterozygosity (chtz) in 9 patients. The genotype and zygosity review of all patients led to the following conclusions: DTD is the most common phenotype in Finland due to a Finnish mutation (c.727-1G>C). Outside of Finland, rMED is the most prevalent phenotype, usually associated with R279W in hmz. In contrast, DTD's genotype is usually in chtz. Despite a large number of variants (38), just 8 are recurrent (R279W, C653S, c.-26+2T>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. (AU) | |
| FAPESP's process: | 15/22145-6 - Contribution to the clinical and etiological study of the skeletal dysplasias and dysostosis in Brazil |
| Grantee: | Denise Pontes Cavalcanti |
| Support Opportunities: | Regular Research Grants |