Congenital limb deficiency: Genetic investigation of 44 individuals presenting mainly longitudinal defects in isolated or syndromic forms

Author(s):Show less -

da Rocha, Leticia Alves ^[1] ; Lacerda Pires, Lucas Vieira ^[1] ; Yamamoto, Guilherme Lopes ^{[1, 2]} ; Magliocco Ceroni, Jose Ricardo ^[1] ; Honjo, Rachel Sayuri ^[1] ; Franca Bisneto, Edgard de Novaes ^[3] ; Nunes Oliveira, Luiz Antonio ^[4] ; Rosenberg, Carla ^[2] ; Victorino Krepischi, Ana Cristina ^[2] ; Passos-Bueno, Maria Rita ^[2] ; Kim, Chong Ae ^[1] ; Bertola, Debora Romeo ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Hosp Clin, Fac Med, Inst Crianca, Genet Unit, Av Dr Eneas de Carvalho Aguiar 647, BR-05403000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Human Genome & Stem Cell Res Ctr, Inst Biociencias, Dept Genet & Biol Evolut, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Orthoped & Traumatol Inst, Hosp Clin, Fac Med, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Crianca, Radiol, Hosp Clin, Fac Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: Clinical Genetics; v. 100, n. 5 AUG 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC