Functional monosomy of 6q27‐qter and functional disomy of Xpter‐p22.11 due to X;6 translocation with an atypical X‐inactivation pattern
Functional monosomy of 6q27‐qter and functional disomy of Xpter‐p22.11 due to X;6 translocation with an atypical X‐inactivation pattern
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由于具有非典型 Xâ 失活模式的 X;6 易位，导致 6q27âqter 的功能性单体和 Xpterâp22 11 的功能性二体性
DOI：
10.1002/ajmg.a.38183
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发表时间：
2017
影响因子：
2
通讯作者：
Nataliya
中科院分区：
文献类型：
--
作者：
Podolska;Kobelt;Albrecht;Sigrid;Hackmann;Andreas;Schröck;Evelin;Kutsche;Kerstin;Di Donato;Nataliya
X染色体失活（XCI）模式在女性中通常是随机的。然而，影响X染色体的染色体重排可由于细胞生长不利而导致XCI偏斜。如果是X;常染色体易位，这通常导致100：0的XCI模式，其中衍生物X是大多数女性中的活性X。从头平衡X;在一名患有小头畸形、小脑蚓部发育不全、心脏缺陷和严重发育迟缓的女性患者中检测到46，X，t（X;6）（p22.1;q27）和完全偏斜的XCI模式（100：0）。我们使用荧光原位杂交技术定位了断裂点区域，发现X连锁基因POLA 1被破坏。POLA 1编码聚合酶α引发酶复合物的催化亚基，该复合物负责启动DNA复制过程; POLA 1的缺失可能与生命不相容。因此，通过RBA显带，我们确定了患者的哪一条X染色体是活跃的。在所有检查的淋巴细胞中，野生型X染色体都是活跃的。我们认为，完全偏向于正常X染色体的XCI是由具有活性衍生物X的细胞死亡引起的，该活性衍生物X是由非功能性POLA 1基因引起的。总之，我们得出结论，6 q27-qter的功能性单体和Xpter-p22. 11的功能性二体是患者临床表型的原因。该病例证明了确定哪一条X染色体失活的重要性，以将女性的临床特征与X染色体常染色体易位与遗传改变的性质相关联。
Pattern of X chromosome inactivation (XCI) is typically random in females. However, chromosomal rearrangements affecting the X chromosome can result in XCI skewing due to cell growth disadvantage. In case of an X;autosome translocation, this usually leads to an XCI pattern of 100:0 with the derivative X being the active one in the majority of females. A de novo balanced X;6 translocation [46,X,t(X;6)(p22.1;q27)] and a completely skewed XCI pattern (100:0) were detected in a female patient with microcephaly, cerebellar vermis hypoplasia, heart defect, and severe developmental delay. We mapped the breakpoint regions using fluorescence in situ hybridization and found the X‐linked genePOLA1to be disrupted.POLA1codes for the catalytic subunit of the polymerase α‐primase complex which is responsible for initiation of the DNA replication process; absence ofPOLA1is probably incompatible with life. Consequently, by RBA banding we determined which of the X chromosomes was the active one in the patient. In all examined lymphocytes the wild‐type X chromosome was active. We propose that completely skewed XCI favoring the normal X chromosome resulted from death of cells with an active derivative X that was caused by a non‐functionalPOLA1gene. In summary, we conclude that functional monosomy of 6q27‐qter and functional disomy of Xpter‐p22.11 are responsible for the clinical phenotype of the patient. This case demonstrates the importance of determining which one of the X chromosomes underwent inactivation to correlate clinical features of a female with an X;autosome translocation with the nature of the genetic alteration.
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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：
1.3
作者：
Kloosterman WP;Hochstenbach R
通讯作者：
Hochstenbach R
影响因子：
--
作者：
Muzi-Falconi M;Giannattasio M;Foiani M;Plevani P
通讯作者：
Plevani P
X 染色体重排的表型：X 失活研究的陷阱。
DOI：
--
发表时间：
2007
期刊：
Pathologie et biologie
影响因子：
--
作者：
C. Schluth;M. Cossée;F. Girard‐Lemaire;N. Carelle;H. Dollfus;E. Jeandidier;E. Flori
通讯作者：
E. Flori
影响因子：
9.8
作者：
Lopez, Luis Carlos;Schuelke, Markus;Hirano, Michio
通讯作者：
Hirano, Michio