Acromelic frontonasal dysostosis and ZSWIM6 mutation: phenotypic spectrum and mosaicism

Clin Genet. 2016 Sep;90(3):270-5. doi: 10.1111/cge.12721.

S R F Twigg ¹, L B Ousager ², K A Miller ¹, Y Zhou ¹, S C Elalaoui ³ ⁴, A Sefiani ³ ⁴, G S Bak ⁵, H Hove ⁶, L K Hansen ⁷, C R Fagerberg ², M Tajir ³ ⁴, A O M Wilkie ¹

Affiliations

1 Clinical Genetics Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
2 Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
3 Human Genomics Center, Faculty of Medicine and Pharmacy of Rabat, Rabat, Morocco.
4 Department of Medical Genetics, National Institute of Health, Rabat, Morocco.
5 Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark.
6 Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
7 Department of Paediatrics, Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.

PMID: 26706854 DOI: 10.1111/cge.12721

Abstract

Acromelic frontonasal dysostosis (AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities. A single recurrent heterozygous missense substitution in ZSWIM6, encoding a protein of unknown function, was previously shown to underlie this disorder in four unrelated cases. Here we describe four additional individuals from three families, comprising two sporadic subjects (one of whom had no limb malformation) and a mildly affected female with a severely affected son. In the latter family we demonstrate parental mosaicism through deep Sequencing of DNA isolated from a variety of tissues, which each contain different levels of mutation. This has important implications for genetic counselling.

Keywords

ZSWIM6; frontonasal malformation; mosaicism; preaxial polydactyly.

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