Yonsei Med J.  2013 Jul;54(4):1053-1057. 10.3349/ymj.2013.54.4.1053.

Novel Mutations in the UNC13D Gene Carried by a Chinese Neonate with Hemophagocytic Lymphohistiocytosis

• Chen Y
• Wang Z
• Cheng Y
• Tang Y

• KMID: 2158245
• DOI: http://doi.org/10.3349/ymj.2013.54.4.1053

Abstract

Hemophagocytic lymphohistiocytosis (HLH) in different ethnicities has been described in the literature, but few cases in patients of Chinese descent have been reported. Here, we describe the case of a Chinese neonate presenting with HLH carrying novel, compound heterozygous mutations of the UNC13D gene, including [c.2295_2298delGCAG, p.Glu765Aspfs*27] in exon 23, c.-250C>T, c.1+30G>A, c.279C>T, c.888G>C, c.18+36A>G, c.20-48T>C, c.1977C>T, c.2296C>T, c.24-46C>T, c.26-9_26-8insC, c.2599A>G, c.28+48C>T and c.3198A>G, some of which have not been reported in the literature. Cytokine profile analyses were performed in this patient, and the results were consistent with our previous findings in HLH patients. Cytokine profile monitoring may be helpful in differentiating among various clinical phases of HLH.

Keyword

FHL; hemophagocytic lymphohistiocytosis; UNC13D; CD107a; cytokine monitoring

MeSH Terms

Asian Continental Ancestry Group/genetics
Cytokines/blood
Heterozygote
Humans
Infant, Newborn
Lymphohistiocytosis, Hemophagocytic/drug therapy/*genetics
Male
Membrane Proteins/*genetics
*Mutation
Cytokines
Membrane Proteins

Figure

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  Fig. 1 Sequencing results of UNC13D gene in a Chinese male neonate and his parents. Genomic DNA sequencing results showed the patient and his mother had heterozygous point mutation c.2296C>T (A), which caused shifted splicing site in the transcription process and in mRNA level manifested as a frameshift mutation c.2295_2298delGCAG (B). In protein level, it lead to a premature stop codon p.Glu765Aspfs*27 and encoded truncated protein munc13-4 (1-792).

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  Fig. 2 The perforin concentration (A) and CD107a positivity before and after K562 cell stimulation (B) in NK cells of this patient and his parents. HLH, hemophagocytic lymphohistiocytosis; PE, phycoerythrin.

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