Open AccessGenetic Counselling Pitfall: Co-Occurrence of an 11.8-Mb Xp22 Duplication and an Xp21.2 Duplication Disrupting IL1RAPL1
Author(s) -
Nicolas Chatron,
Lucie Thibault,
James Lespinasse,
Audrey Labalme,
Caroline Schluth-Bolard,
Marianne Till,
Patrick Edery,
Renaud Touraine,
Vincent Des Portes,
Gaëtan Lesca,
Damien Sanlaville
Publication year - 2017
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000479455
Subject(s) - proband , gene duplication , genetics , karyotype , copy number variation , sister , medicine , biology , chromosome , mutation , genome , gene , sociology , anthropology
We report a 3-generation family in which 2 Xp copy number variations (CNVs) co-segregate. The proband presented with syndromic intellectual disability. The CNV had been revealed by conventional karyotyping, identifying a large Xp22 duplication causing an Xp functional disomy. Family studies found that this duplication was inherited from the proband's mother and was also present in one of his sisters. This sister had conventional karyotyping performed during pregnancy with a normal result. Postnatally, her child, the proband's nephew, presented with autism spectrum disorders. aCGH revealed a 339-kb IL1RAPL1 duplication. Overall, the proband, his mother, and one of his sisters all harboured both CNVs, while his other sister and the 2 sons of each sister only carried the IL1RAPL1 intragenic duplication. As seen in this family, we emphasise the importance of small CNV detection, the pathogenicity of IL1RAPL1 exonic duplications in male carriers, and the difficulties for genetic counselling with the risk of double diagnosis in a single patient.