Congenital limb deficiency: Genetic investigation of 44 individuals presenting mainly longitudinal defects in isolated or syndromic forms. Issue 5 (9th August 2021)

• Record Type: Journal Article
• Authors: da Rocha, Letícia Alves; Pires, Lucas Vieira Lacerda; Yamamoto, Guilherme Lopes; Magliocco Ceroni, José Ricardo; Honjo, Rachel Sayuri; de Novaes França Bisneto, Edgard; Oliveira, Luiz Antônio Nunes; Rosenberg, Carla; Krepischi, Ana Cristina Victorino; Passos‐Bueno, Maria Rita; Kim, Chong Ae; Bertola, Débora Romeo
• Is Part Of: Clinical genetics. Volume 100:Issue 5(2021)
• Page Start: 615
• Page End: 623
• Publication Date: 2021-08-09
• Subjects: congenital anomalies -- congenital limb deficiency -- genetic disorders -- next‐generation sequencing; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.14041
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract: Congenital limb deficiency (CLD), one of the most common congenital anomalies, is characterized by hypoplasia/aplasia of one or more limb bones and can be isolated or syndromic. The etiology in CLD is heterogeneous, including environmental and genetic factors. A fraction remains with no etiological factor identified. We report the study of 44 Brazilian individuals presenting isolated or syndromic CLD, mainly with longitudinal defects. Genetic investigation included particularly next‐generation sequencing (NGS) and/or chromosomal microarray. The overall diagnostic yield was 45.7%, ranging from 60.9% in the syndromic to 16.7% in the non‐syndromic group. In TAR syndrome, a common variant in 3´UTR of RBM8A, in trans with 1q21.1 microdeletion, was detected, corroborating the importance of this recently reported variant in individuals of African ancestry. NGS established a diagnosis in three individuals in syndromes recently reported or still under delineation (an acrofacial dysostosis, Coats plus and Verheij syndromes), suggesting a broader phenotypic spectrum in these disorders. Although a low rate of molecular detection in non‐syndromic forms was observed, it is still possible that variants in non‐coding regions and small CNVs, not detected by the techniques applied in this study, could play a role in the etiology of CLD. Abstract :