Identification of a novel nonsense mutation in the UNC13D gene from a patient
with hemophagocytic lymphohistiocytosis: a case report
#MMPMID29783935
Hu X
; Liu D
; Jiang X
; Gao B
; Chen C
BMC Med Genet
2018[May]; 19
(1
): 82
PMID29783935
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BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous and
potentially fatal disease that presents symptoms of persistent fever,
splenomegaly and cytopenia. Primary HLH is identified as an autosomal recessive
disorder with causative genes including HPLH1, PRF1, UNC13D, STX11 and STXBP2.
CASE PRESENTATION: Here, we reported an 8-month-old female patient with compound
heterozygosity in the UNC13D gene. The patient, who presented typical symptoms,
was diagnosed with HLH based on HLH-2004 guidelines. High-throughput amplicon
sequencing for the full-length exon, including a 5 bp padding region and 6
HLH-related genes, was performed to identify the pathogenic mutations in this
patient. In all, 9 heterozygous variations were detected, namely, 7 nonpathogenic
SNPs, one nonsense mutation (NM_199242.2:c.2206C > T, p.Gln736X), and one
splicing mutation (NM_199242.2:c.2709 + 1G > A). These two mutations were
considered pathogenic according to previous studies and functional prediction. A
two-generation pedigree analysis based on Sanger sequencing was performed to
confirm the result. CONCLUSION: Compound heterozygosity in the UNC13D gene was
identified in trans and considered a causative mutation in a female patient with
HLH. The nonsense mutation (NM_199242.2:c.2206C > T, p.Gln736X) was novel in
cases of HLH. Our data expand the spectrum of HLH-related mutations in China and
demonstrate the potential of high-throughput amplicon sequencing in the diagnosis
of HLH.
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