DOCK6 mutations are responsible for a distinct autosomal-recessive variant of Adams-Oliver syndrome associated with brain and eye anomalies.

Abstract

Adams-Oliver syndrome (AOS) is characterized by the association of aplasia cutis congenita with terminal transverse limb defects, often accompanied by additional cardiovascular or neurological features. Both autosomal-dominant and autosomal-recessive disease transmission have been observed, with recent gene discoveries indicating extensive genetic heterogeneity. Mutations of the DOCK6 gene were first described in autosomal-recessive cases of AOS and only five DOCK6-related families have been reported to date. Recently, a second type of autosomal-recessive AOS has been attributed to EOGT mutations in three consanguineous families. Here, we describe the identification of 13 DOCK6 mutations, the majority of which are novel, across 10 unrelated individuals from a large cohort comprising 47 sporadic cases and 31 AOS pedigrees suggestive of autosomal-recessive inheritance. DOCK6 mutations were strongly associated with structural brain abnormalities, ocular anomalies, and intellectual disability, thus suggesting that DOCK6-linked disease represents a variant of AOS with a particularly poor prognosis.

• Authors: Maja Sukalo, Felix Tilsen, Hülya Kayserili, Dietmar Müller, Beyhan Tüysüz, Deborah M Ruddy, Emma Wakeling, Karen Helene Ørstavik, Katie M Snape, Richard Trembath, Maryse De Smedt, Nathalie van der Aa, Martin Skalej, Stefan Mundlos, Wim Wuyts, Laura Southgate, Martin Zenker
• Journal: Human mutation (Hum Mutat) Vol. 36 Issue 6 Pg. 593-8 (Jun 2015) ISSN: 1098-1004 [Electronic] United States
• PMID: 25824905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 WILEY PERIODICALS, INC.

Chemical References

• Guanine Nucleotide Exchange Factors

Topics

• Adolescent
• Brain (abnormalities, pathology)
• Child
• Child, Preschool
• Ectodermal Dysplasia (diagnosis, genetics)
• Eye Abnormalities (genetics)
• Female
• Genes, Recessive
• Genetic Association Studies
• Guanine Nucleotide Exchange Factors (genetics)
• Humans
• Infant
• Infant, Newborn
• Limb Deformities, Congenital (diagnosis, genetics)
• Magnetic Resonance Imaging
• Male
• Mutation
• Scalp Dermatoses (congenital, diagnosis, genetics)
• Tomography, X-Ray Computed
• Young Adult