Chediak-Higashi syndrome with early developmental delay resulting from paternal heterodisomy of chromosome 1.
Chediak-Higashi syndrome with early developmental delay resulting from paternal heterodisomy of chromosome 1.
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DOI：
10.1002/ajmg.a.33389
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发表时间：
2010-06
影响因子：
2
通讯作者：
Huizing, Marjan
中科院分区：
文献类型：
--
作者：
Manoli, Irini;Golas, Gretchen;Westbroek, Wendy;Vilboux, Thierry;Markello, Thomas C.;Introne, Wendy;Maynard, Dawn;Pederson, Ben;Tsilou, Ekaterini;Jordan, Michael B.;Hart, P. Suzanne;White, James G.;Gahl, William A.;Huizing, Marjan
关键词：
Chediak-Higashi综合征（CHS）是一种罕见的常染色体隐性遗传病，其特征是可变皮肤白化病，免疫缺陷，轻度出血素质和淋巴细胞增殖加速状态。溶酶体相关细胞器膜功能异常可导致多种细胞类型（包括粒细胞、黑素细胞和血小板）内大囊泡的积聚。本报告描述了一例严重的CHS病例，由1号染色体父本异位导致LYST/CHS1基因中迄今为止报道的最远端无义突变（p.E3668X，外显子50）的纯合性。突变位于CHS1蛋白的WD40区。患者的成纤维细胞未表达可检测到的CHS1。除了表现出典型的CHS症状外，患者还表现出张力低下和整体发育迟缓，这引起了人们对异位的其他影响的关注。通过比较基因组杂交，鉴定了亲本和母本6q14.2 ~ 6q14.3位点间存在747kb的重复。SNP基因分型显示，在1号染色体的交叉断点附近，没有额外的全染色体或节段性同工二体区域或其他剂量变化。揭示单独的常染色体隐性原因的发育迟缓，或父亲异源性的加性效应，可能是该患者表型严重程度的基础。
Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease characterized by variable oculocutaneous albinism, immunodeficiency, mild bleeding diathesis and an accelerated lymphoproliferative state. Abnormal lysosome-related organelle membrane function leads to the accumulation of large intracellular vesicles in several cell types, including granulocytes, melanocytes, and platelets. This report describes a severe case of CHS resulting from paternal heterodisomy of chromosome 1, causing homozygosity for the most distal nonsense mutation (p.E3668X, exon 50) reported to date in the LYST/CHS1 gene. The mutation is located in the WD40 region of the CHS1 protein. The patient’s fibroblasts expressed no detectable CHS1. Besides manifesting the classical CHS findings, the patient exhibited hypotonia and global developmental delays, raising concerns about other effects of heterodisomy. An interstitial 747kb duplication on 6q14.2 to 6q14.3 was identified in the propositus and paternal samples by comparative genomic hybridization. SNP genotyping revealed no additional whole chromosome or segmental isodisomic regions or other dosage variations near the crossover breakpoints on chromosome 1. Unmasking of a separate autosomal recessive cause of developmental delay, or an additive effect of the paternal heterodisomy, could underlie the severity of the phenotype in this patient.
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影响因子：
2
作者：
Dobyns, William B.;Mirzaa, Ghayda;Christian, Susan L.;Petras, Kristin;Roseberry, Jessica;Clark, Gary D.;Curry, Cynthia J. R.;McDonald-McGinn, Donna;Medne, Livija;Zackai, Elaine;Parsons, Julie;Zand, Dina J.;Hisama, Fuki M.;Walsh, Christopher A.;Leventer, Richard J.;Martin, Christa L.;Gajecka, Marzena;Shaffer, Lisa G.
通讯作者：
Shaffer, Lisa G.
影响因子：
4.7
作者：
Andersen, Claus Lindbjerg;Wiuf, Carsten;Orntoft, Torben Falck
通讯作者：
Orntoft, Torben Falck
影响因子：
9.8
作者：
Gelb, BD;Willner, JP;Desnick, RJ
通讯作者：
Desnick, RJ
影响因子：
9.8
作者：
Heilstedt, HA;Ballif, BC;Shaffer, LG
通讯作者：
Shaffer, LG
影响因子：
4.1
作者：
Fassihi, H;Wessagowit, V;McGrath, JA
通讯作者：
McGrath, JA