SLC26A2 was first associated with autosomal recessive achondrogenesis type 1B as early as 1996 (Superti-Furga et al., PMID: 8528239). This disorder is perinatal lethal and includes clinical features such as extremely short limbs, fingers, and toes; hypoplasia of the thorax, protuberant abdomen, fetal hydrops, flat face, and a short and thick neck (GeneReviews, Bonafé et al., 2013). However, radiographic analysis and histopathology are also important in arriving at a diagnosis. At least 8 unique variants (including missense, nonsense, and frameshift variants as well as in-frame indels) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 8 probands in 3 publications (PMID: 8528239, 9637425, 8702490). More evidence is available in the literature; however, the maximum score for genetic evidence has been reached. Of note, variants in this gene have also been shown to cause atelosteogenesis type 2, diastrophic dysplasia, and recessive multiple epiphyseal dysplasia, which comprise a spectrum of phenotypes (depending on level of residual sulfate transport) and have been definitively associated with SLC26A2. This gene-disease association is supported by a knock-out mouse model, expression studies, and in vitro functional assays. In summary, SLC26A2 is definitively associated with autosomal recessive achondrogenesis type 1B. This curation was approved by the Skeletal Disorders Gene Curation Expert Panel (GCEP) on 8/3/2020.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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