Tetrasomy 21pter‐q22.11: molecular, cytogenetic, and clinical findings
Tetrasomy 21pter‐q22.11: molecular, cytogenetic, and clinical findings
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21pter-q22.11 四体：分子、细胞遗传学和临床发现
DOI：
10.1034/j.1399-0004.1999.550414.x
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发表时间：
1999
影响因子：
3.5
通讯作者：
I. Slavutsky
中科院分区：
文献类型：
--
作者：
R. Cerretini;V. Luccerini;M. Stivel;V. Bañares;I. Aranda;L. Alba;O. Pivetta;I. Slavutsky
唐氏综合症（DS）是最常见的人类遗传性疾病，发生在1/600-800活产婴儿。尽管它通常是由额外的21号染色体的存在引起的，但人们对额外染色体导致疾病的方式知之甚少。据我们所知，只有2例活产婴儿报告了无镶嵌现象的21号四体，这2例婴儿均具有典型的DS畸形体征（1，2）。在这里，我们描述了一个新的情况下，男性婴儿部分四体21，造成额外的假双着丝粒染色体21 [psu dic（21）]，没有DS表型。先证者是健康非血缘父母的第五个孩子。出生时，母亲46岁，父亲52岁。出生体重为3300 g。转诊，在9.2岁，是精神和语言障碍。体格检查显示短头畸形、圆脸、睑裂水平、鼻梁高、下唇突出、耳位正常、耳轮根穿过耳甲、生殖器肥大。皮纹分析正常。按照表型-基因型相关性方案对该儿童进行检查（3）。除阴茎长度（+4 SD）和睾丸体积（6 ml）外，其他身体测量值均在正常范围内。心电图（EKG）、脑电图（EEG）、眼科评估和脑干听觉诱发电位均正常。脑计算机断层扫描（CT）和磁共振成像（MRI）证实短头畸形，但其他方面正常。我们的患者的临床症状与Jackon列表中的症状进行了比较（4），在DS的10个最具鉴别力的特征中，只有一个是短头畸形。表型评分为0.0126（DS：0.044 - 0.127），因此与DS诊断不一致。根据坦纳的方法（5）、激素谱（6）和头颅MRI，特发性性早熟在9.2岁时被诊断。睾丸超声检查显示睾丸正常。在11.1岁时，先证者已达到青春期坦纳V期，成年睾丸体积（20 ml）和阴茎长度（7）。开始促性腺激素释放激素（GnRH）激动剂治疗。这些发现在健康男性儿童中并不常见，仅在2名DS男孩中观察到（8），其中原发性性腺缺陷很常见（9）。在10岁时，心理检查（特曼测试）显示中度智力迟钝（智商37），他的智力水平约为3岁。视觉建构能力和视觉技能相当于5年的水平。在语言上，他继续明显的困难，他的可理解的讲话被限制在几个字。我们患者的Cu/Zn SOD 1平均浓度（13090.5 mg/ml红细胞）显示相对于正常人群（84.095.7 mg/ml）增加了54.7%，相对于21三体患者（125.096.8 mg/ml）增加了6.5%，提示剂量增加了50%。核型分析显示，额外的假双着丝粒双卫星染色体，这似乎是21号染色体的起源，在所有100个分析的细胞。(Fig. 1a）。用探针WCP 21和D13 Z1/D21 Z1（ONCOR）进行的荧光原位杂交（FISH）分析证实其在整个长度上源自21号染色体并且具有双着丝粒性质。用探针D21 S55、36 D3、8A 4/19 C7和667 B10在标记物上不存在杂交信号。用探针280 B1在psu dic（21）上的杂交信号比在正常染色体21上的大，表明该位点在标记染色体上以双倍剂量存在。(Fig. 1 b）。因此，根据我们的细胞遗传学、细胞分子学和SOD 1结果，认为psu dic（21）上的断点位于基因座SOD 1和D21 S404之间，均位于q22.11。因此，我们的病人的核型显示部分四体的区域21 pter-q22.11，包括SOD 1基因座。其余区域，从q22.11到端粒，存在于正常的二倍体拷贝数中。核型为间-
To the Editor: Down’s syndrome (DS) is the most frequent human genetic disorder, occurring in 1/600–800 live births. Although it is usually caused by the presence of an extra chromosome 21, there is minimal understanding of the way in which the additional chromosome causes the disease. To our knowledge, tetrasomy 21 without mosaicism has been reported in only 2 liveborn infants, both with classic dysmorphic signs of DS (1, 2). Here, we describe a new case of a male infant with a partial tetrasomy 21, resulting from an extra pseudodicentric chromosome 21 [psu dic(21)], without DS phenotype. The proband is the fifth child of healthy, nonconsanguineous parents. At birth, the mother was 46 and the father was 52 years old. Birth weight was 3300 g. Referral, at age 9.2 years, was for psychomotor and speech retardation. His physical examination showed brachycephaly, round face, horizontal palpebral fissures, high nasal bridge, prominent lower lip, normal set ears with helix root crossing concha, and macrogenitalism. Dermatoglyphic analysis was normal. The child was examined following the protocol of phenotype– genotype correlation (3). Physical measurements, with the exception of penile length (+4 SD) and testicular volume (6 ml), were all in the normal range. Electrocardiogram (EKG), electroencephalogram (EEG), ophthalmological evaluation, and brain stem auditory evoked potentials were normal. Brain computed tomography (CT) and magnetic resonance imaging (MRI) confirmed brachycephaly, but were otherwise normal. The clinical symptoms in our patient were compared with those on Jackon’s list (4) and only one, brachycephaly, of the ten most discriminating features of DS was present. The phenotypic score was 0,0126 (DS: 0,044-0,127) and, therefore, not consistent with a diagnosis of DS. Idiopathic precocious puberty was diagnosed at age 9.2 years, according to the method of Tanner (5), hormone profiles (6), and MRI of the cranium. Testicular ultrasonography revealed normal testes. At age 11.1 years, the proband has reached pubertal Tanner stage V, with an adult testicular volume (20 ml) and penile length (7). Treatment with gonadotrophin-releasing hormone (GnRH) agonist was initiated. These findings are unusual in healthy male children and have only been observed in 2 DS boys (8), in which primary gonadal deficiency is common (9). At age 10 years, the psychological examination (Terman test) indicated a moderate mental retardation (IQ 37), and his mental level was about 3 years. Visuoconstructive ability and visuomotor skills corresponded to a level of 5 years. Linguistically, he continued to function with pronounced difficulty, his intelligible speech being limited to a few words. The Cu/Zn SOD1 mean concentration in our patient (13090.5 mg/ml erytrocytes) showed an increased of 54.7% with respect to the normal population (84.095.7 mg/ml) and of 6.5% with respect to trisomy 21 patients (125.096.8 mg/ml), suggestive of 50% increased dosage. Karyotype analysis revealed an extra pseudodicentric bisatellited chromosome, which appeared to be of chromosome 21 origin, in all 100 analyzed cells. (Fig. 1a). Fluorescence in situ hybridization (FISH) analysis with probes WCP 21 and D13Z1/ D21Z1 (ONCOR) confirmed its derivation from chromosome 21 over the entire length and its dicentric nature. Hybridization signals were absent on the marker with probes D21S55, 36D3, 8A4/19C7, and 667B10. The size of the hybridization signal on psu dic(21) was larger than on the normal chromosomes 21 with probe 280B1, suggesting the presence of this locus in double dose in the marker chromosome.(Fig. 1b). Thus, according to our cytogenetic, cytomolecular, and SOD1 results, the breakpoint on psu dic(21) was considered to be between the loci SOD1 and D21S404, both in q22.11. In consequence, our patient’s karyotype shows a partial tetrasomy for the region 21pter-q22.11, including the SOD1 locus. The remaining region, from q22.11 to the telomere, is present in the normal diploid copy number. The karyotype was inter-
建立唐氏综合症基因型-表型相关性的方案。
影响因子：
9.8
作者：
Epstein,CJ;Korenberg,JR;Annerén,G;Antonarakis,SE;Aymé,S;Courchesne,E;Epstein,LB;Fowler,A;Groner,Y;Huret,JL
通讯作者：
Huret,JL
四体 21 pter-->q22.1 和唐氏综合症：该区域的分子定义。
DOI：
10.1002/ajmg.1320530411
发表时间：
1994
期刊：
American journal of medical genetics
影响因子：
--
作者：
Daumer-Haas,C;Schuffenhauer,S;Walther,JU;Schipper,RD;Porstmann,T;Korenberg,JR
通讯作者：
Korenberg,JR