Feng Yuyu, Huang Yonglan, Zhao Xiaoyuan, Sheng Huiying, Su Xueying, Yin Xi, Li Liu, Zhang Wen
Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, China.
BMC Pediatr. 2024 Dec 23;24(1):830. doi: 10.1186/s12887-024-05223-x.
Mucolipidosis (ML) II and III alpha/beta are lysosomal disorders caused by mutations in the GNPTAB gene which encodes the alpha and beta subunits of the heterohexameric enzyme, N-acetylglucosamine-1-phosphotransferase.
To explore the clinical and molecular characteristics of the 20 ML II and III alpha/beta patients, clinical data was collected and GNPTAB gene was analyzed by nest PCR and direct Sanger-sequencing. The activity of several lysosomal enzymes was measured in the plasma.
Among the 20 ML II and III alpha/beta patients, 6 patients were classified as ML II and 14 as ML III alpha/beta. The main clinical manifestations were joint stiffness, skeletal deformity, mental retardation and short stature. Bone X-ray examination showed radiological changes. The plasma arylsulfatase A and hexosaminidase A enzyme activities increased significantly. Urinary glycosaminoglycan values were normal. We detected mutations in GNPTAB in 35 of 40 alleles (87.5%). Mutation c.2715 + 1G > A and c.2404 C > T (p.Gln802Ter) were the most prevalent variants, accounting for 14.3% and 11.4%, respectively. Five novel mutations c.3335 + 5G > A, c.1284 + 1G > A, c.571 + 4 A > G, c.1634_1635delAA (p.Lys545Serfs*16) and c.1582T > C(p.Cys528Arg) were identified.
Our study expands the spectrum of GNPTAB gene in China. Mutation c.2715 + 1G > A was the most prevalent mutation in our study. The novel mutation c.1284 + 1G > A might be a severe mutation associated with ML II.
黏脂贮积症（ML）II型和III型α/β型是由GNPTAB基因突变引起的溶酶体疾病，该基因编码异源六聚体酶N-乙酰葡糖胺-1-磷酸转移酶的α和β亚基。
为探究20例ML II型和III型α/β型患者的临床和分子特征，收集临床数据并通过巢式PCR和直接桑格测序法分析GNPTAB基因。检测血浆中几种溶酶体酶的活性。
在20例ML II型和III型α/β型患者中，6例被归类为ML II型，14例为ML III型α/β型。主要临床表现为关节僵硬、骨骼畸形、智力发育迟缓及身材矮小。骨骼X线检查显示有影像学改变。血浆芳基硫酸酯酶A和己糖胺酶A的酶活性显著升高。尿糖胺聚糖值正常。我们在40个等位基因中的35个（87.5%）检测到GNPTAB基因突变。突变c.2715+1G>A和c.2404 C>T（p.Gln802Ter）是最常见的变异，分别占14.3%和11.4%。鉴定出5种新突变，即c.3335+5G>A、c.1284+1G>A、c.571+4 A>G、c.1634_1635delAA（p.Lys545Serfs*16）和c.1582T>C（p.Cys528Arg）。
我们的研究扩展了中国GNPTAB基因的突变谱。突变c.2715+1G>A是我们研究中最常见的突变。新突变c.12
