A novel homozygous CHMP1A variant arising from segmental uniparental disomy causes pontocerebellar hypoplasia type 8
A novel homozygous CHMP1A variant arising from segmental uniparental disomy causes pontocerebellar hypoplasia type 8
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节段性单亲二体性产生的新型纯合 CHMP1A 变异导致 8 型脑桥小脑发育不全
DOI：
10.1038/s10038-022-01098-x
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发表时间：
2023
期刊：
影响因子：
3.5
通讯作者：
T. Mizuguchi and N. Matsumoto
中科院分区：
文献类型：
--
作者：
M. Sakamoto;T. Shiiki;S. Matsui;N. Okamoto;E. Koshimizu;N. Tsuchida;Y. Uchiyama;K. Hamanaka;A. Fujita;S. Miyatake;K. Misawa;T. Mizuguchi and N. Matsumoto
桥小脑发育不全(PCH)目前分为16个亚型。使用主要是下一代测序，已经在多达24个与PCH相关的基因中识别出致病变异。PCH 8型(PCH8)是一种罕见的异质性疾病。其临床表现包括严重的发育迟缓、肌肉张力增加、小头畸形和磁共振成像(MRI)异常，如大脑白质减少、穹隆变薄、脑干和小脑发育不良。到目前为止，在来自4个家族(MIM：164010)的7名PCH8患者中，只发现了CHMP1A1基因(MIM：164010)的两个变异体，NM_002768.5：C.88 C >； T(p.Glu30*)和c.28-13 G >； A。CHMP1A是运输所需的内体分选复合体(ESCRT-III)的一个亚单位，调节细胞外小泡的形成和释放。双等位基因CHMP1功能丧失会损害ESCRT-III介导的细胞外小泡释放，从而导致发育中大脑的祖细胞增殖受损。在此，我们报告了一例PCH8患者，他有一个纯合的CHMP1突变，c.122delA(p.Asn41Metf*2)，该突变源于节段性单亲二体。尽管我们的患者有与先前报道的患者相似的MRI表现，但没有进展，我们报告了一些新的神经和发育方面的发现，这些发现扩大了我们对CHMP1变异相关临床后果的了解。
Pontocerebellar hypoplasia (PCH) is currently classified into 16 subgroups. Using mostly next-generation sequencing, pathogenic variants have been identified in as many as 24 PCH-associated genes. PCH type 8 (PCH8) is a rare heterogeneous disorder. Its clinical presentation includes severe development delay, increased muscle tone, microcephaly, and magnetic resonance imaging (MRI) abnormalities such as reduced cerebral white matter, a thin corpus callosum, and brainstem and cerebellar hypoplasia. To date, only two variants in theCHMP1Agene (MIM: 164010), NM_002768.5: c.88 C > T (p.Glu30*) and c.28–13 G > A, have been identified homozygously in seven patients with PCH8 from four families (MIM: 614961).CHMP1Ais a subunit of the endosomal sorting complex required for transport III (ESCRT-III), which regulates the formation and release of extracellular vesicles. BiallelicCHMP1Aloss of function impairs the ESCRT-III-mediated release of extracellular vesicles, which causes impaired progenitor proliferation in the developing brain. Herein, we report a patient with PCH8 who had a homozygousCHMP1Avariant, c.122delA (p.Asn41Metfs*2), which arose from segmental uniparental disomy. Although our patient had similar MRI findings to those of previously reported patients, with no progression, we report some novel neurological and developmental findings that expand our knowledge of the clinical consequences associated withCHMP1Avariants.
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影响因子：
30.8
作者：
Mochida, Ganeshwaran H.;Ganesh, Vijay S.;de Michelena, Maria I.;Dias, Hugo;Atabay, Kutay D.;Kathrein, Katie L.;Huang, Hsuan-Ting;Hill, R. Sean;Felie, Jillian M.;Rakiec, Daniel;Gleason, Danielle;Hill, Anthony D.;Malik, Athar N.;Barry, Brenda J.;Partlow, Jennifer N.;Tan, Wen-Hann;Glader, Laurie J.;Barkovich, A. James;Dobyns, William B.;Zon, Leonard I.;Walsh, Christopher A.
通讯作者：
Walsh, Christopher A.
影响因子：
3.5
作者：
Kahrizi, Kimia;Hu, Hao;Ropers, Hans-Hilger
通讯作者：
Ropers, Hans-Hilger
影响因子：
9.8
作者：
Fromer, Menachem;Moran, Jennifer L.;Purcell, Shaun M.
通讯作者：
Purcell, Shaun M.
影响因子：
8.8
作者：
Coulter ME;Dorobantu CM;Lodewijk GA;Delalande F;Cianferani S;Ganesh VS;Smith RS;Lim ET;Xu CS;Pang S;Wong ET;Lidov HGW;Calicchio ML;Yang E;Gonzalez DM;Schlaeger TM;Mochida GH;Hess H;Lee WA;Lehtinen MK;Kirchhausen T;Haussler D;Jacobs FMJ;Gaudin R;Walsh CA
通讯作者：
Walsh CA
影响因子：
16.6
作者：
McCullough J;Colf LA;Sundquist WI
通讯作者：
Sundquist WI