TY - JOUR
T1 - Split hand/foot malformation associated with 20p12.1 deletion: A case report
AU - Ruaud, Lyse
AU - Flöttmann, Ricarda
AU - Spielmann, Malte
AU - Escande, Fabienne
AU - Van Maldergem, Lionel
AU - Mundlos, Stefan
AU - Piard, Juliette
N1 - Funding Information:
M.S. was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) ( SP1532/3-1 , SP1532/4-1 , SP1532/5-1 ).
Publisher Copyright:
© 2019
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/4
Y1 - 2020/4
N2 - Split hand/foot malformation (SHFM) or ectrodactyly is a rare congenital disorder affecting limb development characterized by clinical and genetic heterogeneity. SHFM is usually inherited as an autosomal dominant trait with incomplete penetrance. Isolated and syndromic forms are described. The extent of associated malformations is highly variable and multiple syndromes with clinical and genetic overlap have been described. We report here a 28 year-old man presenting with SHFM, sparse hair and widespread freckles. Array-CGH identified a 450 kb de novo 20p12.1 microdeletion encompassing three exons (exon 6 to 8) of MACROD2. Although MACROD2 mutations have not been associated with limb malformation until now, it is located next to KIF16B, which is involved in fibroblast growth factor receptor (FGFR) signaling. Additionally, the deletion encompassed a histone modification H3K27ac mark, known as a provider of quantitative readout of promoter and enhancer activity during human limb development. Altogether, these findings suggest that the 20p12.1 CNV is causative of SHFM in the present case through disturbance of regulatory elements functioning.
AB - Split hand/foot malformation (SHFM) or ectrodactyly is a rare congenital disorder affecting limb development characterized by clinical and genetic heterogeneity. SHFM is usually inherited as an autosomal dominant trait with incomplete penetrance. Isolated and syndromic forms are described. The extent of associated malformations is highly variable and multiple syndromes with clinical and genetic overlap have been described. We report here a 28 year-old man presenting with SHFM, sparse hair and widespread freckles. Array-CGH identified a 450 kb de novo 20p12.1 microdeletion encompassing three exons (exon 6 to 8) of MACROD2. Although MACROD2 mutations have not been associated with limb malformation until now, it is located next to KIF16B, which is involved in fibroblast growth factor receptor (FGFR) signaling. Additionally, the deletion encompassed a histone modification H3K27ac mark, known as a provider of quantitative readout of promoter and enhancer activity during human limb development. Altogether, these findings suggest that the 20p12.1 CNV is causative of SHFM in the present case through disturbance of regulatory elements functioning.
UR - http://www.scopus.com/inward/record.url?scp=85075874785&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/18e4028a-06c9-3ea7-bcbd-e5dda2f313c7/
U2 - 10.1016/j.ejmg.2019.103805
DO - 10.1016/j.ejmg.2019.103805
M3 - Journal articles
C2 - 31698100
AN - SCOPUS:85075874785
SN - 1769-7212
VL - 63
SP - 103805
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
IS - 4
M1 - 103805
ER -
