Three new patients with Steel syndrome and a Puerto Rican specific COL27A1 mutation

Abstract

Steel syndrome was initially described by H. H. Steel in 1993 in Puerto Rico, at which time he described the clinical findings required for diagnosis. The responsible gene, COL27A1, was identified in 2015 (Gonzaga‐Jauregui et al., European Journal of Human Genetics, 2015;23:342–346). Eleven patients have previously been described with Steel syndrome and homozygous COL27A1 mutations, with eight having an apparent founder mutation, p.Gly697Arg. We describe three more patients identified at Einstein Medical Center Philadelphia and St. Christopher's Hospital for Children (Philadelphia, PA) diagnosed with Steel syndrome. All three are of Puerto Rican ancestry with the previously described founder mutation and had either hip dislocations or hip dysplasia. Radial head dislocation was only identified in one patient while short stature and scoliosis were noted in two of these patients. There are now 51 patients in the literature with Steel syndrome, including the 3 patients in this article, and 14 patients with a genetically confirmed Steel syndrome diagnosis.

Functional biology of the Steel syndrome founder allele and evidence for clan genomics derivation of COL27A1 pathogenic alleles worldwide

“…Due to the absence of reported consanguinity, which was further verified genetically by the lack of sharing of large segments of homozygosity beyond the region around the COL27A1 gene delineating a common haplotype harboring the c.2089G>C (p.Gly697Arg) variant, at the time we proposed that this variant was the molecular cause of the disease and that it was likely a founder allele in individuals of Puerto Rican ancestry. Since then, we and others [ 5 , 23 ] have confirmed that homozygosity for this missense variant is indeed the molecular defect that causes the skeletal abnormalities observed in STLS.…”

“…We also performed allele specific genotyping of the c.2089G>C (p.Gly697Arg) variant in suspected Steel syndrome families ascertained since our initial study, including a duo composed of the unaffected mother and her reportedly affected 7-year-old son with clinical and radiological findings of STLS, whom was recently published separately along with other two STLS patients [ 23 ]. The affected proband (BAB8472) was found to be homozygous for the STLS variant and his unaffected mother is, as anticipated, a heterozygous carrier.…”