Gene Mutation of Interleukin-2 Receptor Common Gamma Chain in Four Male Infants with X-Linked Severe Combined Immunodeficiency

doi:10.3877/cma.j.issn.1673-5250.2014.03.016

Objective

To analyse the relationship between clinical manifestations and the mutation of interleukin-2 receptor common gamma chain (IL-2RG) mutation of X-linked severe combined immunodeficiency (SCID) caused by IL-2RG.

Methods

From May 2010 to September 2012, four boys who were clinically suspected as X-linked SCID were enrolled in this study. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of West China Second University Hospital, Sichuan University.Informed consent was obtained from each participants' parents. IL-2RG mutation were detected and analyzed in four patients and their family members.

Results

Four boys were all suffered by severe pulmonary infection (severe pneumonia) and demonstrated to have absence of thymus or dysplastic thymus by chest X-ray film. Among them, three patients had tuberculosis infection after bacilli Calmette-Guerin (BCG) vaccination (75%), two patients had family history (50%), and all patients suffered lymphopenia (100%). All 4 male infants were demonstrated to be X-linked SCID due to the mutation of IL-2RG, including 2 patients with nonsense mutations (50%, c. 711.G>A, p. W237X and c. 578.G>A, p. W193X, respectively), one missense mutation (25%, c. 173C>A, p. P58Q), and 1 splice site mutation (25%, IVS5-2 G>T). The linear relatives of 3 patients and maternal relatives were detected the mutation of IL-2RG, and 3 patients were demonstrated to have family carriers (75%) and one patient was suffered by de novo mutation (25%).

Conclusions

The detection of IL-2RG gene mutation can confirm clinical diagnosis of X-linked SCID which is critical for patients to take hematopoietic stem cell transplantation as soon as possible to reconstruction of immunity before the fatal infection occurred. The early immune reconstruction can offer the best chance of long term survival.

Key words: Severe combined immunodeficiency, Receptors, interleukin-2, Mutation

表1 4例患儿的临床特征

Table 1 Clinical characterizations of four infants with X-linked SCID

序号	性别	起病年龄(d)	诊断年龄(d)	重症肺炎	持续腹泻	胸腺	PPD皮试	卡介苗接种	家族病史
患儿1	男	120	178	有	有	显著缩小	阴性	接种部位化脓	有^b
患儿2	男	97	141	有	有	无胸腺	阴性	全身散播性结核感^a	无
患儿3	男	171	213	有	无	无胸腺	阴性	接种部位红肿、破溃	无
患儿4	男	89	102	有	有	无胸腺	阴性	接种部位未见异常^c	有^d

表1 4例患儿的临床特征

Table 1 Clinical characterizations of four infants with X-linked SCID

序号	性别	起病年龄(d)	诊断年龄(d)	重症肺炎	持续腹泻	胸腺	PPD皮试	卡介苗接种	家族病史
患儿1	男	120	178	有	有	显著缩小	阴性	接种部位化脓	有^b
患儿2	男	97	141	有	有	无胸腺	阴性	全身散播性结核感^a	无
患儿3	男	171	213	有	无	无胸腺	阴性	接种部位红肿、破溃	无
患儿4	男	89	102	有	有	无胸腺	阴性	接种部位未见异常^c	有^d

表2 4例患儿血常规检测结果(×10⁹/L)

Table 2 Results of complete blood count of four infants with X-linked SCID(×10⁹/L)

序号	WBC计数	中性粒细胞	淋巴细胞	Hb(g/L)	PLT计数
患儿1	4.50～7.20	3.08～5.47	0.54～0.86	74.00～90.00	283.00～376.00
患儿2	2.20	1.54	0.15	119.00	35.00
患儿3	8.80	6.10	2.50	122.00	279.00
患儿4	7.30	5.48	1.39	102.00	483.00

表2 4例患儿血常规检测结果(×10⁹/L)

Table 2 Results of complete blood count of four infants with X-linked SCID(×10⁹/L)

序号	WBC计数	中性粒细胞	淋巴细胞	Hb(g/L)	PLT计数
患儿1	4.50～7.20	3.08～5.47	0.54～0.86	74.00～90.00	283.00～376.00
患儿2	2.20	1.54	0.15	119.00	35.00
患儿3	8.80	6.10	2.50	122.00	279.00
患儿4	7.30	5.48	1.39	102.00	483.00

表3 4例患儿免疫学检测结果(%)

Table 3 Results of immunology detection of four infants with X-linked SCID(%)

序号	CD₃	CD₄	CD₈	CD₁₉⁺	CD₁₆⁺/CD₅₆⁺	IgG(g/L)	IgA(g/L)	IgM(g/L)	IgE(IU/mL)
患儿1	0.00(50.00～84.00)	0.00(27.00～51.00)	0.00(15.00～44.00)	68.00(5.00～18.00)	29.00(7.00～40.00)	6.60(3.05～8.87)	0.14(0.11～0.45)	0.19(0.31～0.85)	2.60(<150.00)
患儿2	0.30(48.00～75.00)	0.20(33.00～58.00)	0.10(11.00～25.00)	75.00(14.00～39.00)	0.10(2.00～14.00)	8.13(2.60～6.90)	0.15(0.03～0.82)	0.12(0.15～1.09)	1.50(0.00～7.20)
患儿3	0.15(64.62～77.80)	0.07(32.69～44.23)	0.02(24.81～35.99)	91.70(6.38～12.46)	1.67(14.40～30.27)	3.90(4.10～10.80)	179.00(130.00～820.00)	591.00(480.00～2 280.00)	8.00(<150.00)
患儿4	3.70(48.00～75.00)	0.90(33.00～58.00)	2.60(11.00～25.00)	92.10(14.00～39.00)	1.40(2.00～14.00)	6.34(2.60～6.90)	0.03(0.03～0.82)	0.59(0.15～1.09)	241.4(0.00～7.20)

表3 4例患儿免疫学检测结果(%)

Table 3 Results of immunology detection of four infants with X-linked SCID(%)

序号	CD₃	CD₄	CD₈	CD₁₉⁺	CD₁₆⁺/CD₅₆⁺	IgG(g/L)	IgA(g/L)	IgM(g/L)	IgE(IU/mL)
患儿1	0.00(50.00～84.00)	0.00(27.00～51.00)	0.00(15.00～44.00)	68.00(5.00～18.00)	29.00(7.00～40.00)	6.60(3.05～8.87)	0.14(0.11～0.45)	0.19(0.31～0.85)	2.60(<150.00)
患儿2	0.30(48.00～75.00)	0.20(33.00～58.00)	0.10(11.00～25.00)	75.00(14.00～39.00)	0.10(2.00～14.00)	8.13(2.60～6.90)	0.15(0.03～0.82)	0.12(0.15～1.09)	1.50(0.00～7.20)
患儿3	0.15(64.62～77.80)	0.07(32.69～44.23)	0.02(24.81～35.99)	91.70(6.38～12.46)	1.67(14.40～30.27)	3.90(4.10～10.80)	179.00(130.00～820.00)	591.00(480.00～2 280.00)	8.00(<150.00)
患儿4	3.70(48.00～75.00)	0.90(33.00～58.00)	2.60(11.00～25.00)	92.10(14.00～39.00)	1.40(2.00～14.00)	6.34(2.60～6.90)	0.03(0.03～0.82)	0.59(0.15～1.09)	241.4(0.00～7.20)

表4 4例患儿IL-2RG基因突变测定结果

Table 3 The gene mutations of IL-2RG of four infants with X-SCID

序号	突变部位	基因突变	氨基酸异常	突变类型	家族携带者
患儿1	Exon5	g.2559.G>A；c.711.G>A	p.W237X	无义突变	母亲、姐姐、姨妈、表姐
患儿2	Exon4	g.2426.G>A；c.578.G>A	p.W193X	无义突变	母亲
患儿3	Exon2	g.840C>A；c.173C>A	p.P58Q	错义突变	无
患儿4	Intron5	IVS5-2 G>T	－	拼接位点突变	母亲

表4 4例患儿IL-2RG基因突变测定结果

Table 3 The gene mutations of IL-2RG of four infants with X-SCID

序号	突变部位	基因突变	氨基酸异常	突变类型	家族携带者
患儿1	Exon5	g.2559.G>A；c.711.G>A	p.W237X	无义突变	母亲、姐姐、姨妈、表姐
患儿2	Exon4	g.2426.G>A；c.578.G>A	p.W193X	无义突变	母亲
患儿3	Exon2	g.840C>A；c.173C>A	p.P58Q	错义突变	无
患儿4	Intron5	IVS5-2 G>T	－	拼接位点突变	母亲

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