Grave aortic aneurysmal dilatation in DOCK8 deficiency

Mutairi, Muna Al; Al‐Mousa, Hamoud; Al-Saud, Bander; Hawwari, Abbas; Aljoufan, Mansour; AlWesaibi, Abdulkarim; Al‐Halees, Zohair; Al‐Mayouf, Sulaiman M.

doi:10.3109/14397595.2013.874735

Cited by 8 publications

(5 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The defective actin accumulates in natural killer (NK) cells and cripple their cytotoxicity function ( 10 ). Although DOCK8-deficient patients were first described as suffering from a type of Hyper-IgE syndrome ( 11 ), it soon became clear that this is a distinct entity of graver prognosis ( 12 ). Here, we describe the case of a DOCK8-deficient school-age boy with normal IgE serum levels, who nevertheless had other signs and findings that allowed suspecting the diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Case Report: DOCK8 Deficiency Without Hyper-IgE in a Child With a Large Deletion

et al. 2021

View full text Add to dashboard Cite

Autosomal recessive (AR) DOCK8 deficiency is a well-known actinopathy, a combined primary immune deficiency with impaired actin polymerization that results in altered cell mobility and immune synapse. DOCK8-deficient patients present early in life with eczema, viral cutaneous infections, chronic mucocutaneous candidiasis, bacterial pneumonia, and abscesses, together with eosinophilia, thrombocytosis, lymphopenia, and variable dysgammaglobulinemia that usually includes Hyper-IgE. In fact, before its genetic etiology was known, patients were described as having a form of Hyper-IgE syndrome, a name now deprecated in favor of genetic defects. We describe a school-age male patient with a clinical picture suggestive of DOCK8 deficiency, except for high serum IgE or a family history: early onset, failure to thrive, eczema, warts, condyloma, bronchiolitis, pneumonia, recurrent otitis media, bronchiectasis, candidiasis, leukocytosis, eosinophilia, high IgA, low IgG, and low CD4+ T cells. We were able to confirm the diagnosis through protein expression and whole-exome sequencing. We review the clinical, laboratory, and genetic features of 200 DOCK8-deficient patients; at least 4 other patients have had no elevated IgE, and about 40% do not have Hyper-IgE (above 1,000 IU/mL). Despite this, the constellation of signs, symptoms, and findings allow the suspicion of DOCK8 deficiency and other actinopathies.

show abstract

Section: Introductionmentioning

confidence: 99%

Case Report: DOCK8 Deficiency Without Hyper-IgE in a Child With a Large Deletion

et al. 2021

View full text Add to dashboard Cite

show abstract

“…DOCK8 encodes a protein implicated in the regulation of the actin cytoskeleton 119 , and DOCK8 mutations cause autosomal recessive hyper-IgE syndrome 120 . One reported case of a homozygous 129 kb deletion in this region was associated with Graves’s disease and aortic aneurysm 121 . However, several deletions of DOCK8 are recorded in the DGV for unaffected individuals, therefore the CNVs in EqSCM 14 and 28 were categorised as TBB (thought to be benign).…”

Section: Discussionmentioning

confidence: 99%

Copy number variants implicate cardiac function and development pathways in earthquake-induced stress cardiomyopathy

Lacey

Doudney

Bridgman

et al. 2018

Sci Rep

View full text Add to dashboard Cite

The pathophysiology of stress cardiomyopathy (SCM), also known as takotsubo syndrome, is poorly understood. SCM usually occurs sporadically, often in association with a stressful event, but clusters of cases are reported after major natural disasters. There is some evidence that this is a familial condition. We have examined three possible models for an underlying genetic predisposition to SCM. Our primary study cohort consists of 28 women who suffered SCM as a result of two devastating earthquakes that struck the city of Christchurch, New Zealand, in 2010 and 2011. To seek possible underlying genetic factors we carried out exome analysis, genotyping array analysis, and array comparative genomic hybridization on these subjects. The most striking finding was the observation of a markedly elevated rate of rare, heterogeneous copy number variants (CNV) of uncertain clinical significance (in 12/28 subjects). Several of these CNVs impacted on genes of cardiac relevance including RBFOX1, GPC5, KCNRG, CHODL, and GPBP1L1. There is no physical overlap between the CNVs, and the genes they impact do not appear to be functionally related. The recognition that SCM predisposition may be associated with a high rate of rare CNVs offers a novel perspective on this enigmatic condition.

show abstract

“…144 One reported case of a homozygous 129kb deletion in this region was associated with Graves’s disease and aortic aneurysm. 145 However, several deletions of DOCK8 are recorded in the DGV for unaffected individuals, therefore the CNVs in EqSCM 14 and 28 were categorised as TBB (thought to be benign). The approximately160kb duplication in EqSCM 28 was larger than the 44kb deletion in EqSCM 14, and it encompassed a second gene, KANK1 .…”

Section: Discussionmentioning

confidence: 99%

Copy number variants implicate cardiac function and development pathways in earthquake-induced stress cardiomyopathy

Lacey

Doudney²,

Bridgman

et al. 2017

Preprint

View full text Add to dashboard Cite

Grave aortic aneurysmal dilatation in DOCK8 deficiency

Cited by 8 publications

References 15 publications

Case Report: DOCK8 Deficiency Without Hyper-IgE in a Child With a Large Deletion

Case Report: DOCK8 Deficiency Without Hyper-IgE in a Child With a Large Deletion

Copy number variants implicate cardiac function and development pathways in earthquake-induced stress cardiomyopathy

Copy number variants implicate cardiac function and development pathways in earthquake-induced stress cardiomyopathy

Contact Info

Product

Resources

About