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Pathogenic variant in NFIX gene affecting three sisters due to paternal mosaicism
Author(s) -
Sihombing Nydia Rena Benita,
Winarni Tri Indah,
Bokhoven Hans,
Burgt Ineke,
Leeuw Nicole,
Faradz Sultana M. H.
Publication year - 2020
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61835
Subject(s) - genetics , nonsense , macrocephaly , exome sequencing , phenotype , gene , intellectual disability , biology
We present a family with three girls presenting similar dysmorphic features, including overgrowth, intellectual disability, macrocephaly, prominent forehead, midface retrusion, strabismus, and scoliosis. Both parents were unaffected, suggesting the presence of an autosomal recessive syndrome. Following exome sequencing, a heterozygous nonsense variant was identified in the NFIX gene in all three siblings. The father appeared to have a low‐grade (7%) mosaicism for this variant in his blood. Previously, de novo pathogenic variants in NFIX have been identified in Marshall–Smith syndrome and Malan syndrome, which share distinctive phenotypic features shared with the patients of the present family. This case emphasizes the importance of further molecular analysis especially in familial cases, to exclude the possibility of parental mosaicism.