未经证实:SLC26A2/DTDST基因中的致病变异导致以下表型谱:软骨缺失1B(ACG1B),非骨生成2(AO2),舒张性发育不良(DTD),和隐性多发性骨phy发育不良(rMED),前两个是致命的。这里,我们报道了SLC26A2/DTDST相关疾病的基因型-表型相关性的队列和综合文献综述.
UNASSIGNED:通过Sanger测序或下一代测序(NGS)对当地患者进行基因分型。我们回顾了有关表型的文献数据,合子,和基因型平行。
未经证实:当地队列招募了12名患者,包括具有类似Desbuquois表型的人。除了一个显示双等位基因突变,然而,在携带ACG1B的胎儿中仅发现一个等位基因突变.文献综述确定了42篇文章,基因型和接合性的分析包括12名当地患者。
未经证实:R279W变异体在当地患者中最为普遍。2例rMED患者为纯合性(hmz),9例患者为复合杂合性(chtz)。对所有患者的基因型和接合性回顾得出以下结论:由于芬兰突变,DTD是芬兰最常见的表型(c.727-1G>C)。在芬兰以外,rMED是最普遍的表型,通常与hmz中的R279W相关。相比之下,DTD的基因型通常为chtz。尽管有大量的变体(38),只有8个是经常性的(R279W,C653S,c.-26+2T>C,R178*,K575Sfs*10,V340del,G663R,T512K)。hmz中的最后3个导致致死表型。芬兰突变仅在芬兰以外的chtz中发现,与所有4种经典表型相关。p.R178*和p.K575Sfs*10变体应被视为致死突变,因为两者主要用致死表型描述,并且从未在hmz中报道。9例仅有一个突变等位基因的患者的存在表明,这些患者的另一个等位基因中的其他突变仍需要揭示。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.