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. 2014 Jul;35(7):824-7.
doi: 10.1002/humu.22563. Epub 2014 May 21.

TCIRG1-associated congenital neutropenia

Vahagn Makaryan  1 , Elisabeth A Rosenthal, Audrey Anna Bolyard, Merideth L Kelley, Jennifer E Below, Michael J Bamshad, Kathryn M Bofferding, Joshua D Smith, Kati Buckingham, Laurence A Boxer, Julia Skokowa, Karl Welte, Deborah A Nickerson, Gail P Jarvik, David C Dale; UW Center for Mendelian Genomics
Affiliations

TCIRG1-associated congenital neutropenia

Vahagn Makaryan et al. Hum Mutat. 2014 Jul.

Abstract

Severe congenital neutropenia (SCN) is a rare hematopoietic disorder, with estimated incidence of 1 in 200,000 individuals of European descent, many cases of which are inherited in an autosomal dominant pattern. Despite the fact that several causal genes have been identified, the genetic basis for >30% of cases remains unknown. We report a five-generation family segregating a novel single nucleotide variant (SNV) in TCIRG1. There is perfect cosegregation of the SNV with congenital neutropenia in this family; all 11 affected, but none of the unaffected, individuals carry this novel SNV. Western blot analysis show reduced levels of TCIRG1 protein in affected individuals, compared to healthy controls. Two unrelated patients with SCN, identified by independent investigators, are heterozygous for different, rare, highly conserved, coding variants in TCIRG1.

Keywords: SCN; TCIRG1; V-ATPase; congenital neutropenia.

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Conflict of interest statement

Conflict of Interest Disclosure:

All authors of this manuscript declare no competing financial interests.

Figures

Figure 1
Figure 1
A. Electropherogram depicting TCIRG1 novel mutation (the N above the G nucleotide at pos 342 in this electropherogram is computer generated error and should be labeled as G) B. Western blot analysis of TCIRG1expression:

  1. down regulated levels of 45kDa TCIRG1 product in PB mononuclear cells of 3 patients (26%, 49%, 35% respectively) compared to healthy individual.

  2. Identical expression level of TCIRG1-isoa. (n=3)

See this image and copyright information in PMC

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