X-linked intellectual disability type Nascimento is a clinically distinct, probably underdiagnosed entity.
X-linked intellectual disability type Nascimento is a clinically distinct, probably underdiagnosed entity.
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X连锁的智力残疾型Nascimento是一种临床上不同的，可能未被诊断的实体。
DOI：
10.1186/1750-1172-8-146
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发表时间：
2013-09-21
影响因子：
3.7
通讯作者：
Kuechler A
中科院分区：
文献类型：
--
作者：
Czeschik JC;Bauer P;Buiting K;Dufke C;Guillén-Navarro E;Johnson DS;Koehler U;López-González V;Lüdecke HJ;Male A;Morrogh D;Rieß A;Tzschach A;Wieczorek D;Kuechler A
X连锁智力残疾Nascimento型（MIM #300860），由UBE 2A突变引起（MIM *312180），其特征是颅面畸形（同温层畸形、眶上嵴突出、深陷、杏仁状眼、鼻梁凹陷、鼻小柱突出、鼻翼发育不全和巨口畸形）、皮肤异常（多毛症、粘液水肿外观、甲营养不良）、小阴茎、中度至重度智力残疾（ID）、运动延迟、言语受损/缺失和癫痫发作。迄今为止，文献中仅报道了五种家族性点突变和四种不同的缺失，包括UBE 2A。我们提出了另外八个人从五个家庭与UBE 2A相关的ID -三名男性从一个血缘家庭，其中我们确定了一个小的缺失只有7.1 kb，包括前三个外显子的UBE 2A，两个相关的男性与UBE 2A错义突变的外显子4，一个病人与从头无义突变的外显子6，和两个散发的男性较大的缺失，包括UBE 2A。所有受影响的男性个体具有典型的临床表型，所有携带者女性不受影响，并在血液中呈现完全偏斜的X失活。我们的结论是1）。X连锁智力残疾类型Nascimento是一种临床上非常独特的实体，迄今为止可能诊断不足。2.）的情况。到目前为止，所有携带家族性UBE 2A畸变的女性都有完全偏斜的X染色体失活，临床上不受影响。在向这些家庭提供咨询时应考虑到这一点。3.）第三章在分析之前，应仔细检查阵列的覆盖范围，因为并非所有阵列在特定基因座处都具有足够的分辨率，或者应应用替代定量方法以避免遗漏小的缺失。
X-linked intellectual disability type Nascimento (MIM #300860), caused by mutations in UBE2A (MIM *312180), is characterized by craniofacial dysmorphism (synophrys, prominent supraorbital ridges, deep-set, almond-shaped eyes, depressed nasal bridge, prominent columella, hypoplastic alae nasi, and macrostomia), skin anomalies (hirsutism, myxedematous appearance, onychodystrophy), micropenis, moderate to severe intellectual disability (ID), motor delay, impaired/absent speech, and seizures. Hitherto only five familial point mutations and four different deletions including UBE2A have been reported in the literature. We present eight additional individuals from five families with UBE2A associated ID - three males from a consanguineous family, in whom we identified a small deletion of only 7.1 kb encompassing the first three exons of UBE2A, two related males with a UBE2A missense mutation in exon 4, a patient with a de novo nonsense mutation in exon 6, and two sporadic males with larger deletions including UBE2A. All affected male individuals share the typical clinical phenotype, all carrier females are unaffected and presented with a completely skewed X inactivation in blood. We conclude that 1.) X-linked intellectual disability type Nascimento is a clinically very distinct entity that might be underdiagnosed to date. 2.) So far, all females carrying a familial UBE2A aberration have a completely skewed X inactivation and are clinically unaffected. This should be taken in to account when counselling those families. 3.) The coverage of an array should be checked carefully prior to analysis since not all arrays have a sufficient resolution at specific loci, or alternative quantitative methods should be applied not to miss small deletions.
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影响因子：
3.5
作者：
Honda, Shozo;Orii, Koji O.;Inazawa, Johji
通讯作者：
Inazawa, Johji
影响因子：
5.3
作者：
Sharp, A;Robinson, D;Jacobs, P
通讯作者：
Jacobs, P
影响因子：
5.2
作者：
Gecz, Jozef;Turner, Gillian;Partington, Michael
通讯作者：
Partington, Michael
影响因子：
5.8
作者：
Koressaar, Triinu;Remm, Maido
通讯作者：
Remm, Maido
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作者：
de Leeuw, Nicole;Bulk, Saskia;de Brouwer, Arjan P. M.
通讯作者：
de Brouwer, Arjan P. M.