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Mol Cytogenet. 2015 Mar 26;8:20. doi: 10.1186/s13039-015-0126-7. eCollection 2015.

Familial intragenic duplication of ANKRD11 underlying three patients of KBG syndrome.

Author information

1
Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, via Ariosto 13, Milano, 20145 Italy.
2
Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano, via Ariosto 13, Milano, 20145 Italy ; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, via Viotti 3/5, Milano, 20133 Italy.
3
U.O.S Clinical Genetics and Pediatrics, MBBM Foundation San Gerardo Hospital, Via G. Pergolesi, 33, Monza, (MB) 20052 Italy.

Abstract

BACKGROUND:

KBG syndrome, a rare autosomal disorder characterised by distinctive craniofacial and skeletal features and developmental delay, is caused by haploinsufficiency of the ANKRD11 gene.

RESULTS:

Here we describe two siblings with multiple symptoms characteristic of KBG and their mother with a milder phenotype. In the siblings, array-based comparative genomic hybridization (array CGH) identified an intragenic microduplication affecting ANKRD11 that was absent from the parents' array CGH profiles. Microsatellite analysis revealed the maternal origin of the rearrangement and interphase fluorescent in situ hybridization (i-FISH) experiments identified the rearrangement in low-level mosaicism in the mother. Molecular characterisation of the duplication allele demonstrated the presence of two mutant ANKRD11 transcripts containing a premature stop codon and predicting a truncated non-functional protein.

CONCLUSIONS:

Similarly to deletions and point mutations, this novel pathogenetic rearrangement causes haploinsufficiency of ANKRD11, resulting in KBG syndrome.

KEYWORDS:

ANKRD11 intragenic duplication; Genotype–phenotype correlations; KBG syndrome; Low-level mosaicism

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