Abstract
IMPORTANCE: Mutations in the CERC1 gene associated with deficiency in the ADA2 protein (DADA2) have been implicated in the pathogenesis of cutaneous polyarteritis nodosa (cPAN) and early-onset vasculopathy. DADA2 is not only limited to cPAN and vasculopathy but also includes immunodeficiency that affects several cellular compartments, including B cells; however, some patients appear to have a more indolent, skin-limited disease. OBSERVATIONS: In this report, we describe 2 white siblings (female and male) with a history of cPAN with DADA2 as a result of novel compound heterozygous mutations inherited in trans in the CECR1 gene (c.37-39del [p.K13del] and c.1159C>A [p.N328K]). The onset of disease was earlier in the female sibling than the male sibling although both were diagnosed as having cPAN in early childhood. The disease is associated with a more significant immunodeficiency and other systemic symptoms in the female than the male sibling. CONCLUSIONS AND RELEVANCE: These findings suggest a genetic cause of cPAN in some patients. Therefore, DADA2 should be considered in patients with cPAN, specifically in those whose conditions are diagnosed at an early age, regardless of their ethnicity, presence or absence of systemic symptoms, or a family history of the disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1230-1234 |
| Number of pages | 5 |
| Journal | JAMA Dermatology |
| Volume | 151 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2015 |
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ASJC Scopus subject areas
- Dermatology
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Dermatologic features of ADA2 deficiency in cutaneous polyarteritis nodosa. / Santiago, Tania M Gonzalez; Zavialov, Andrey; Saarela, Janna; Seppanen, Mikko; Reed, Ann M.; Abraham, Roshini S.; Gibson, Lawrence E.
In: JAMA Dermatology, Vol. 151, No. 11, 01.11.2015, p. 1230-1234.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dermatologic features of ADA2 deficiency in cutaneous polyarteritis nodosa
AU - Santiago, Tania M Gonzalez
AU - Zavialov, Andrey
AU - Saarela, Janna
AU - Seppanen, Mikko
AU - Reed, Ann M.
AU - Abraham, Roshini S.
AU - Gibson, Lawrence E.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - IMPORTANCE: Mutations in the CERC1 gene associated with deficiency in the ADA2 protein (DADA2) have been implicated in the pathogenesis of cutaneous polyarteritis nodosa (cPAN) and early-onset vasculopathy. DADA2 is not only limited to cPAN and vasculopathy but also includes immunodeficiency that affects several cellular compartments, including B cells; however, some patients appear to have a more indolent, skin-limited disease. OBSERVATIONS: In this report, we describe 2 white siblings (female and male) with a history of cPAN with DADA2 as a result of novel compound heterozygous mutations inherited in trans in the CECR1 gene (c.37-39del [p.K13del] and c.1159C>A [p.N328K]). The onset of disease was earlier in the female sibling than the male sibling although both were diagnosed as having cPAN in early childhood. The disease is associated with a more significant immunodeficiency and other systemic symptoms in the female than the male sibling. CONCLUSIONS AND RELEVANCE: These findings suggest a genetic cause of cPAN in some patients. Therefore, DADA2 should be considered in patients with cPAN, specifically in those whose conditions are diagnosed at an early age, regardless of their ethnicity, presence or absence of systemic symptoms, or a family history of the disease.
AB - IMPORTANCE: Mutations in the CERC1 gene associated with deficiency in the ADA2 protein (DADA2) have been implicated in the pathogenesis of cutaneous polyarteritis nodosa (cPAN) and early-onset vasculopathy. DADA2 is not only limited to cPAN and vasculopathy but also includes immunodeficiency that affects several cellular compartments, including B cells; however, some patients appear to have a more indolent, skin-limited disease. OBSERVATIONS: In this report, we describe 2 white siblings (female and male) with a history of cPAN with DADA2 as a result of novel compound heterozygous mutations inherited in trans in the CECR1 gene (c.37-39del [p.K13del] and c.1159C>A [p.N328K]). The onset of disease was earlier in the female sibling than the male sibling although both were diagnosed as having cPAN in early childhood. The disease is associated with a more significant immunodeficiency and other systemic symptoms in the female than the male sibling. CONCLUSIONS AND RELEVANCE: These findings suggest a genetic cause of cPAN in some patients. Therefore, DADA2 should be considered in patients with cPAN, specifically in those whose conditions are diagnosed at an early age, regardless of their ethnicity, presence or absence of systemic symptoms, or a family history of the disease.
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UR - http://www.scopus.com/inward/citedby.url?scp=84946865962&partnerID=8YFLogxK
U2 - 10.1001/jamadermatol.2015.1635
DO - 10.1001/jamadermatol.2015.1635
M3 - Article
C2 - 26131734
AN - SCOPUS:84946865962
VL - 151
SP - 1230
EP - 1234
JO - JAMA Dermatology
JF - JAMA Dermatology
SN - 2168-6068
IS - 11
ER -