Disease Spectrum and Gene Variation Analysis of Neonatal Inherited Metabolic Diseases in Gansu Region

doi:10.12280/gjszjk.20240239

Abstract

Abstract:

Objective: To retrospectively analyze the disease spectrum, incidence rate and gene variation spectrum of neonatal inherited metabolic diseases in Gansu province, and to explore the genetic characteristics of these diseases. Methods: 213 786 cases with the dried blood spots were screened by tandem mass spectrometry from January 2021 to December 2023. The suspected positive children were diagnosed by urine gas chromatography mass spectrometry or (and) high-throughput gene sequencing. The spectrum of disease, incidence and gene variation were analyzed. Results: 145 cases were diagnosed in 189 high risk newborns, including 15 kinds of inherited metabolic diseases. The total incidence of inherited metabolic diseases in Gansu was 1/1 474, among which 68.28% (99 cases) were hyperphenylalanine. A total of 268 mutation sites related to 20 mutation genes were found, such as some hot spot mutations: c.728G>A, c.611A>G mutations in PAH gene, c.609G>A, c.567dupT mutations in MMACHC gene, and the new variants not reported: c.298G>T mutation in MMACHC gene, c.2000A>G mutation in MUT gene, c.734-7A>G mutation in MMAA gene. Conclusions: Mass spectrometry combined with gene detection can effectively explore the genetic characteristics of inherited metabolic diseases, which provides data support for follow-up clinical diagnosis and genetic counseling of these diseases.

Key words: Tandem mass spectrometry, Gas chromatography-mass spectrometry, High-throughput nucleotide sequencing, Genetic diseases, inborn

LIU Fu-rong, WANG Xing, LI Yan-ting, ZHANG Chuan, GUO Yuan-yuan, HUI Ling, HAO Sheng-ju. Disease Spectrum and Gene Variation Analysis of Neonatal Inherited Metabolic Diseases in Gansu Region[J]. Journal of International Reproductive Health/Family Planning, 2024, 43(5): 378-383.

Figures/Tables 5

References 21

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疾病谱	确诊数（例）	构成比（%）	发病率（%）
高苯丙氨酸血症	99	68.28	1/2 159
甲基丙二酸血症	24	16.55	1/8 908
瓜氨酸血症	5	3.45	1/42 757
枫糖尿病	2	1.38	1/106 893
3-甲基巴豆酰辅酶A羧化酶缺乏症	2	1.38	1/106 893
肉碱酰基转移酶缺乏症	2	1.38	1/106 893
极长链酰基辅酶A脱氢酶缺乏症	2	1.38	1/106 893
鸟氨酸氨甲酰转移酶缺乏症	2	1.38	1/106 893
丙酸血症	1	0.69	1/213 786
3-甲基戊烯二酸尿症	1	0.69	1/213 786
酪氨酸血症	1	0.69	1/213 786
半乳糖血症	1	0.69	1/213 786
原发性肉碱缺乏症	1	0.69	1/213 786
甘氨酸脑病	1	0.69	1/213 786
β酮硫解酶缺乏症	1	0.69	1/213 786
合计	145	100.00	1/1 474

疾病谱	确诊数（例）	构成比（%）	发病率（%）
高苯丙氨酸血症	99	68.28	1/2 159
甲基丙二酸血症	24	16.55	1/8 908
瓜氨酸血症	5	3.45	1/42 757
枫糖尿病	2	1.38	1/106 893
3-甲基巴豆酰辅酶A羧化酶缺乏症	2	1.38	1/106 893
肉碱酰基转移酶缺乏症	2	1.38	1/106 893
极长链酰基辅酶A脱氢酶缺乏症	2	1.38	1/106 893
鸟氨酸氨甲酰转移酶缺乏症	2	1.38	1/106 893
丙酸血症	1	0.69	1/213 786
3-甲基戊烯二酸尿症	1	0.69	1/213 786
酪氨酸血症	1	0.69	1/213 786
半乳糖血症	1	0.69	1/213 786
原发性肉碱缺乏症	1	0.69	1/213 786
甘氨酸脑病	1	0.69	1/213 786
β酮硫解酶缺乏症	1	0.69	1/213 786
合计	145	100.00	1/1 474

外显子	变异频次（次）	外显子变异率（%）
exon7	61	41.50
exon11	19	12.93
exon6	17	11.56
exon12	11	7.48
exon2	11	7.48
exon3	9	6.12
exon5	6	4.08
exon9	6	4.08
exon8	4	2.72
exon10	3	2.04
合计	147	100.00

外显子	变异频次（次）	外显子变异率（%）
exon7	61	41.50
exon11	19	12.93
exon6	17	11.56
exon12	11	7.48
exon2	11	7.48
exon3	9	6.12
exon5	6	4.08
exon9	6	4.08
exon8	4	2.72
exon10	3	2.04
合计	147	100.00

外显子/ 内含子	核苷酸变化	氨基酸变化	变异频次	位点变异率（%）
exon7	c.728G>A	p.R243Q	32	17.58
exon6	c.611A>G	p.Y204C	11	6.04
exon7	c.721C>T	p.R241C	8	4.40
exon2	c.158G>A	p.R53H	8	4.40
exon12	c.1238G>C	p.R413P	7	3.85
exon3	c.331C>T	p.R111X	5	2.75
exon7	c.782G>A	p.R261Q	5	2.75
exon10	c.971T>A	p.I324N	4	2.20
exon11	c.1068C>A	p.Y356X	4	2.20
exon11	c.1197A>T	p.V399V	4	2.20
exon6	c.688G>A	p.V230I	4	2.20
exon12	c.1256A>G	p.Q419R	3	1.65
exon6	c.694C>T	p.Q232X	3	1.65
exon9	c.940C>A	p.P314T	3	1.65
exon11	c.1199G>A	p.R400K	2	1.10
exon12	c.1252A>C	p.T418P	2	1.10
exon3	c.194T>C	p.I65T	2	1.10
exon5	c.482T>C	p.F161S	2	1.10
exon7	c.722G>A	p.R241H	2	1.10
exon7	c.737C>T	p.A246V	2	1.10
exon7	c.740G>T	p.G247V	2	1.10
exon8	c.898G>T	p.A300S	2	1.10
intron4	c.442-1G>A	IVS4-1G>A	8	4.40
intron7	c.842+2T>A	IVS7+2T>A	5	2.75