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

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

doi:10.1002/humu.22795

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

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

Research output: Contribution to journal › Article › peer-review

36 Citations (Scopus)

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.

Original language	English
Pages (from-to)	593-8
Number of pages	6
Journal	Human Mutation
Volume	36
Issue number	6
DOIs	https://doi.org/10.1002/humu.22795
Publication status	Published - Jun 2015

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Sukalo, M., Tilsen, F., Kayserili, H., Müller, D., Tüysüz, B., Ruddy, D. M., Wakeling, E., Ørstavik, K. H., Snape, K. M., Trembath, R., De Smedt, M., van der Aa, N., Skalej, M., Mundlos, S., Wuyts, W., Southgate, L., & Zenker, M. (2015). DOCK6 mutations are responsible for a distinct autosomal-recessive variant of Adams-Oliver syndrome associated with brain and eye anomalies. Human Mutation, 36(6), 593-8. https://doi.org/10.1002/humu.22795

@article{96787ffc173e4c90a37d064f8d4e1b04,

title = "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.",

keywords = "Adolescent, Brain, Child, Child, Preschool, Ectodermal Dysplasia, Eye Abnormalities, Female, Genes, Recessive, Genetic Association Studies, Guanine Nucleotide Exchange Factors, Humans, Infant, Infant, Newborn, Limb Deformities, Congenital, Magnetic Resonance Imaging, Male, Mutation, Scalp Dermatoses, Tomography, X-Ray Computed, Young Adult",

author = "Maja Sukalo and Felix Tilsen and H{\"u}lya Kayserili and Dietmar M{\"u}ller and Beyhan T{\"u}ys{\"u}z and Ruddy, {Deborah M} and Emma Wakeling and {\O}rstavik, {Karen Helene} and Snape, {Katie M} and Richard Trembath and {De Smedt}, Maryse and {van der Aa}, Nathalie and Martin Skalej and Stefan Mundlos and Wim Wuyts and Laura Southgate and Martin Zenker",

note = "{\textcopyright} 2015 WILEY PERIODICALS, INC.",

year = "2015",

month = jun,

doi = "10.1002/humu.22795",

language = "English",

volume = "36",

pages = "593--8",

journal = "Human Mutation",

issn = "1059-7794",

publisher = "Wiley",

number = "6",

}

Sukalo, M, Tilsen, F, Kayserili, H, Müller, D, Tüysüz, B, Ruddy, DM, Wakeling, E, Ørstavik, KH, Snape, KM, Trembath, R, De Smedt, M, van der Aa, N, Skalej, M, Mundlos, S, Wuyts, W, Southgate, L & Zenker, M 2015, 'DOCK6 mutations are responsible for a distinct autosomal-recessive variant of Adams-Oliver syndrome associated with brain and eye anomalies', Human Mutation, vol. 36, no. 6, pp. 593-8. https://doi.org/10.1002/humu.22795

TY - JOUR

T1 - DOCK6 mutations are responsible for a distinct autosomal-recessive variant of Adams-Oliver syndrome associated with brain and eye anomalies

AU - Sukalo, Maja

AU - Tilsen, Felix

AU - Kayserili, Hülya

AU - Müller, Dietmar

AU - Tüysüz, Beyhan

AU - Ruddy, Deborah M

AU - Wakeling, Emma

AU - Ørstavik, Karen Helene

AU - Snape, Katie M

AU - Trembath, Richard

AU - De Smedt, Maryse

AU - van der Aa, Nathalie

AU - Skalej, Martin

AU - Mundlos, Stefan

AU - Wuyts, Wim

AU - Southgate, Laura

AU - Zenker, Martin

PY - 2015/6

Y1 - 2015/6

N2 - 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.

AB - 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.

KW - Adolescent

KW - Brain

KW - Child

KW - Child, Preschool

KW - Ectodermal Dysplasia

KW - Eye Abnormalities

KW - Female

KW - Genes, Recessive

KW - Genetic Association Studies

KW - Guanine Nucleotide Exchange Factors

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Limb Deformities, Congenital

KW - Magnetic Resonance Imaging

KW - Male

KW - Mutation

KW - Scalp Dermatoses

KW - Tomography, X-Ray Computed

KW - Young Adult

U2 - 10.1002/humu.22795

DO - 10.1002/humu.22795

M3 - Article

C2 - 25824905

SN - 1059-7794

VL - 36

SP - 593

EP - 598

JO - Human Mutation

JF - Human Mutation

IS - 6

ER -

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

Abstract

Keywords

UN SDGs

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