<i>DOCK6</i>Mutations Are Responsible for a Distinct Autosomal-Recessive Variant of Adams-Oliver Syndrome Associated with Brain and Eye Anomalies

Sukalo, Maja; Tilsen, Felix; Kayserili, Hülya; Müller, Dietmar; Tüysüz, Beyhan; Ruddy, Deborah; Wakeling, Emma; Ørstavik, Karen Helene; Bramswig, Nuria C.; Snape, Katie; Trembath, Richard; Smedt, Maryse De; Aa, Nathalie Van der; Skalej, Martin; Mundlos, Stefan; Wuyts, Wim; Southgate, Laura; Zenker, Martin

doi:10.1002/humu.22830

Cited by 14 publications

(22 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CMTC was reported in 29% of mutation‐positive patients, while other observed vascular features included defects of pulmonary or portal vasculature, abnormal branching of the carotid artery, and sinus sagittalis thrombosis (Table ). In DOCK6 ‐positive cases, we observed a positive correlation with the presence of brain abnormalities and/or intellectual disability, as previously described (≥91% vs. ≥19%, Table ) (Sukalo et al., ).…”

Section: Resultssupporting

confidence: 87%

“…We identified a total of 13 distinct DOCK6 mutations and two VUS in DOCK6 , all of which have been previously reported by our consortium () (Sukalo et al., ). As expected, all homozygous mutations were present in families with close parental relatedness.…”

Section: Discussionmentioning

confidence: 68%

“…GRCh37 was used as the reference human genome build. The remaining patients were screened by either whole‐exome sequencing (WES, n = 28) or Sanger sequencing ( n = 26) as previously described (Southgate et al., ; Sukalo et al., ). ANNOVAR (Wang, Li, & Hakonarson, ) dbNSFPv3.0.a (Liu, Jian, & Boerwinkle, ) annotation was used for in silico prediction scores, including MutationTaster (Schwarz, Cooper, Schuelke, & Seelow, ), SIFT (Kumar, Henikoff, & Ng, ), PolyPhen2 hvar (Adzhubei et al., ), and CADD () (Kircher et al., ).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort

et al. 2018

Self Cite

View full text Add to dashboard Cite

Adams–Oliver syndrome (AOS) is a rare developmental disorder, characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Autosomal dominant forms of AOS are linked to mutations in ARHGAP31, DLL4, NOTCH1 or RBPJ, while DOCK6 and EOGT underlie autosomal recessive inheritance. Data on the frequency and distribution of mutations in large cohorts are currently limited. The purpose of this study was therefore to comprehensively examine the genetic architecture of AOS in an extensive cohort. Molecular diagnostic screening of 194 AOS/ACC/TTLD probands/families was conducted using next‐generation and/or capillary sequencing analyses. In total, we identified 63 (likely) pathogenic mutations, comprising 56 distinct and 22 novel mutations, providing a molecular diagnosis in 30% of patients. Taken together with previous reports, these findings bring the total number of reported disease variants to 63, with a diagnostic yield of 36% in familial cases. NOTCH1 is the major contributor, underlying 10% of AOS/ACC/TTLD cases, with DLL4 (6%), DOCK6 (6%), ARHGAP31 (3%), EOGT (3%), and RBPJ (2%) representing additional causality in this cohort. We confirm the relevance of genetic screening across the AOS/ACC/TTLD spectrum, highlighting preliminary but important genotype–phenotype correlations. This cohort offers potential for further gene identification to address missing heritability.

show abstract

Section: Resultssupporting

confidence: 87%

Section: Discussionmentioning

confidence: 68%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…CMTC and cardiac malformations are common (20%), while ophthalmological abnormalities occur in <10% 2. Neurological deficits are uncommon, but more severe vascular phenotypes may have developmental problems and seizures 3. Different inheritance patterns are described; autosomal dominant likely in this case in view of paternal history.…”

Section: Descriptionmentioning

confidence: 78%

Adams-Oliver syndrome associated with gastrointestinal malformations

et al. 2016

View full text Add to dashboard Cite

“…DNA sequencing revealed two heterozygous disease‐causing mutations in the DOCK6 gene. The first was a c.4480G>T transversion in exon 35 and the second was a c.5939+2T>C transition in IVS46 resulting in aberrant messenger RNA processing, both of which have been previously reported as DOCK6 mutations associated with AOS . DNA sequencing failed to show mutations in other genes implicated in AOS, including, ARHGAP31 , RBPJ , EOGT , and NOTCH .…”

Section: Case Reportmentioning

confidence: 90%

Adams–Oliver Syndrome Type 2 in Association with Compound Heterozygous DOCK6 Mutations

Jones

Silfvast‐Kaiser

Leake

et al. 2017

Pediatric Dermatology

View full text Add to dashboard Cite

Adams-Oliver syndrome (AOS) is a multiple congenital anomaly syndrome characterized by aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLDs). We present a case of type 2 autosomal recessive AOS associated with heterozygous mutations in the dedicator of cytokinesis 6 (DOCK6) gene, with characteristic findings of ACC, TTLD, intracerebral periventricular calcifications, and polymicrogyria.

show abstract

DOCK6Mutations Are Responsible for a Distinct Autosomal-Recessive Variant of Adams-Oliver Syndrome Associated with Brain and Eye Anomalies

Cited by 14 publications

References 0 publications

Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort

Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort

Adams-Oliver syndrome associated with gastrointestinal malformations

Adams–Oliver Syndrome Type 2 in Association with Compound Heterozygous DOCK6 Mutations

Contact Info

Product

Resources

About