Congenital limb deficiency: Genetic investigation of 44 individuals presenting mainly longitudinal defects in isolated or syndromic forms.
Clin Genet
; 100(5): 615-623, 2021 11.
Article
en En
| MEDLINE
| ID: mdl-34341987
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
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Deformidades Congénitas de las Extremidades
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Predisposición Genética a la Enfermedad
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Estudios de Asociación Genética
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Child, preschool
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Female
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Humans
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Infant
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Male
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Newborn
País/Región como asunto:
America do sul
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Brasil
Idioma:
En
Año:
2021
Tipo del documento:
Article