TY - JOUR
T1 - Phenotypic Characteristics and Copy Number Variants in a Cohort of Colombian Patients with VACTERL Association
AU - Surrallés i Calonge, Jordi
AU - Moreno, O.M.
AU - Sanchez, A.I.
AU - Herreno, A.
AU - Giraldo, G.
AU - Suarez, F.
AU - Prieto, J.C.
AU - Clavijo, A.S.
AU - Olaya, M.
AU - Vargas, Y.
AU - Benitez, J.
AU - Rojas, A.
PY - 2020
Y1 - 2020
N2 - VACTERL association (OMIM 192350) is a heterogeneous clinical condition characterized by congenital structural defects that include at least 3 of the following features: vertebral abnormalities, anal atresia, heart defects, tracheoesophageal fistula, renal malformations, and limb defects. The nonrandom occurrence of these malformations and some familial cases suggest a possible association with genetic factors such as chromosomal alterations, gene mutations, and inherited syndromes such as Fanconi anemia (FA). In this study, the clinical phenotype and its relationship with the presence of chromosomal abnormalities and FA were evaluated in 18 patients with VACTERL association. For this, a G-banded karyotype, array-comparative genomic hybridization, and chromosomal fragility test for FA were performed. All patients (10 female and 8 male) showed a broad clinical spectrum: 13 (72.2%) had vertebral abnormalities, 8 (44.4%) had anal atresia, 14 (77.8%) had heart defects, 8 (44.4%) had esophageal atresia, 10 (55.6%) had renal abnormalities, and 10 (55.6%) had limb defects. Chromosomal abnormalities and FA were ruled out. In 2 cases, the finding of microalterations, namely del(15)(q11.2) and dup(17)(q12), explained the phenotype; in 8 cases, copy number variations were classified as variants of unknown significance and as not yet described in VACTERL. These variants comprise genes related to important cellular functions and embryonic development.
AB - VACTERL association (OMIM 192350) is a heterogeneous clinical condition characterized by congenital structural defects that include at least 3 of the following features: vertebral abnormalities, anal atresia, heart defects, tracheoesophageal fistula, renal malformations, and limb defects. The nonrandom occurrence of these malformations and some familial cases suggest a possible association with genetic factors such as chromosomal alterations, gene mutations, and inherited syndromes such as Fanconi anemia (FA). In this study, the clinical phenotype and its relationship with the presence of chromosomal abnormalities and FA were evaluated in 18 patients with VACTERL association. For this, a G-banded karyotype, array-comparative genomic hybridization, and chromosomal fragility test for FA were performed. All patients (10 female and 8 male) showed a broad clinical spectrum: 13 (72.2%) had vertebral abnormalities, 8 (44.4%) had anal atresia, 14 (77.8%) had heart defects, 8 (44.4%) had esophageal atresia, 10 (55.6%) had renal abnormalities, and 10 (55.6%) had limb defects. Chromosomal abnormalities and FA were ruled out. In 2 cases, the finding of microalterations, namely del(15)(q11.2) and dup(17)(q12), explained the phenotype; in 8 cases, copy number variations were classified as variants of unknown significance and as not yet described in VACTERL. These variants comprise genes related to important cellular functions and embryonic development.
KW - Array-CGH
KW - Chromosomal microalterations
KW - Congenital malformations
KW - Copy-number variants
KW - Fanconi anemia
KW - VACTERL association
U2 - 10.1159/000510910
DO - 10.1159/000510910
M3 - Article
C2 - 33505230
SN - 1661-8769
VL - 11
SP - 271
EP - 283
JO - Molecular Syndromology
JF - Molecular Syndromology
IS - 5-6
ER -