Growth in North American white children with neurofibromatosis 1 (NF1)

OBJECTIVE—To analyse the distributions of and generate growth charts for stature and occipitofrontal circumference (OFC) in neurofibromatosis 1 (NF1) patients.
DESIGN—Cross sectional database survey.
SETTING—The National Neurofibromatosis Foundation International Database (NFDB) includes clinical information on NF1 patients from 14 participating centres in North America.
SUBJECTS—A total of 569 white, North American, NF1 patients, 55% female and 45% male.
MAIN OUTCOME MEASURES—Stature and OFC measurements of NF1 patients were compared to age and sex matched population norms using z score standardisation and centile curves.
RESULTS—The distributions of stature and OFC are shifted and unimodal among NF1 patients; 13% of patients have short stature (2 standard deviations below the population mean) and 24% have macrocephaly (OFC 2 standard deviations above the population mean).
CONCLUSIONS—Alterations of stature and OFC are not limited to NF1 patients with frank short stature or macrocephaly.


Keywords: neurofibromatosis 1; stature; occipitofrontal circumference; macrocephaly     

5′HOXD基因与单纯性马蹄内翻足的相关性分析

目的检测HOXD10、HOXD12、HOXD13基因内4个已知单核苷酸多态(single nucleotide poly-morphisms,SNP)rs2593778、rs847154、rs847151、rs13392701在单纯性马蹄内翻足核心家系中的分布情况,分析各个SNP位点及所构成单倍型与单纯性马蹄内翻足的相关性。方法应用限制性片段长度多态性技术结合测序,分析84个单纯性马蹄内翻足核心家系4个SNP位点基因型;应用ETDT软件统计分析各SNP位点基因型与单纯性马蹄内翻足的相关性;应用TRANSMIT软件构建单倍型并统计分析单倍型频率是否存在差异。结果位于HOXD12基因5′侧翼序列的SNP位点rs847154和位于HOXD13第1外显子的SNP位点rs13392701在单纯性马蹄内翻核心家系中存在传递不平衡(P<0.05);位于HOXD12基因第1外显子的SNP位点rs847151未检测到多态;位于HOXD10第1外显子的SNP位点rs2593778经ETDT分析无统计学意义。结论HOXD12基因5′侧翼序列的SNP位点rs847154和位于HOXD13第1外显子的SNP位点rs13392701与单纯性先天性马蹄内翻足有明显的相关性,提示HOXD12、HOXD13可能是单纯性马蹄内翻足重要的易感基因。     

Skeletal abnormalities in the Apert syndrome

This paper reports on skeletal abnormalities in 38 patients with Apert syndrome. Analysis includes alterations in the shoulders, humeri, elbows, hips, knees, rib cage, and spine (except the cervical spine). Some patients had subacromial dimples and elbow dimples during infancy. Mobility at the glenohumeral joint was limited. Progressive limitation in abduction, forward flexion, and external rotation with growth was virtually a constant finding. The acromioclavicular joint was prominent and sometimes had an angular, pointed appearance clinically. This was often associated with atrophic musculature and winging of the scapulae. Limited elbow mobility was common and usually mild in degree. Decreased elbow extension was most often found with decreased flexion, pronation, and supination occurring less frequently. Limited elbow mobility did not change significantly with growth in contrast to the increasing severity observed in the shoulder joint. Short humeri were a constant finding beyond infancy and genua valga of mild degree were present in many cases. Radiographic examination strongly suggests that the Apert syndrome is characterized by a multiple epiphyseal dysplasia. We found delay in appearance of postnatal ossification centers, particularly in the humeral head, greater tuberosity, capitulum, and radial head. Subsequently, these bones became abnormal in shape. Glenoid dysplasia was observed consistently. The neck of the scapula was very short or absent and the inferior margin of the glenoid cavity was poorly demarcated from the infraglenoid tubercle. The humeral head became oblong in shape with relative prominence of the greater tuberosity which compromised abduction. In the elbow, the capitulum was often small and the radial head was flat in many instances. Subluxation or dislocation of the radial head or angulation of the radial neck was observed in some cases. In the hip joint of some adults, the femoral necks were short and broad with prominence of the greater trochanters. Less common radiographic findings are also discussed. © 1993 Wiley-Liss, Inc.     

Short rib-polydactyly syndrome and pericentric inversion of chromosome 4

We report on a newborn infant with clinical and radiological manifestations of some type of short rib-polydactyly syndrome who died soon after birth. Chromosomal studies on peripheral blood lymphocytes and chondrocytes demonstrated an apparently balanced pericentric inversion of chromosome 4 (present in the mother also). This association may have occurred by chance but, if not, the chromosomal breakpoints could interrupt the gene responsible for short rib-polydactyly syndromes, or else be related to the mechanism of short rib-polydactyly syndromes. © 1994 Wiley-Liss, Inc.     

Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

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Three Kinds of Foamy Cells in the Spleen: Comparative Histochemical and Ultrastructural Studies

By light and electron microscopy, we observed foamy cells in the spleens from a patient with hemolytic anemia due to red cell adenosine deaminase (ADA) overproduction, a patient with rheumatoid arthritis (RA) treated with gold, and patients with idiopathic thrombocytopenic purpura (ITP)

The foamy cells associated with red cell ADA overproduction were essentially similar to Gaucher-like cells described in patients with thalassemia, and it was suggested that the accelerated destruction of red cells was one of the factors responsible for the development of foamy cells. Foamy cells in ITP and RA were closely associated with an increased destruction of platelets in the spleen. Morphologic transitions between phagocytosed platelets and myelinlike materials were traced in these disorders. In RA, however, foamy cells were heterogeneous from an ultrastructural standpoint, with different cytoplasmic inclusions. In addition to myelinlike materials, dense bodies, vacuoles with flocculent materials, and gold were noted in most of foamy cells. As gold compounds are known to inhibit lysosomal enzymes, we surmise that an acquired disturbance in lysosomal digestion is partially responsible for the accumulation of intermediate metabolites.

In the pathogenesis of foamy cells associated with blood cell dyscrasia, the accelerated destruction of blood cells and/or acquired disorders in catabolic pathways within the macrophages are suggested to be the underlying mechanism of an intralysosomal accumulation of incompletely degraded cellular debris.     

Human growth hormone 1 (GH1) gene expression: complex haplotype-dependent influence of polymorphic variation in the proximal promoter and locus control region

The proximal promoter region of the human pituitary expressed growth hormone (GH1) gene is highly polymorphic, containing at least 15 single nucleotide polymorphisms (SNPs). This variation is manifest in 40 different haplotypes, the high diversity being explicable in terms of gene conversion, recurrent mutation, and selection. Functional analysis showed that 12 haplotypes were associated with a significantly reduced level of reporter gene expression whereas 10 haplotypes were associated with a significantly increased level. The former tend to be more prevalent in the general population than the latter (p<0.01), possibly as a consequence of selection. Although individual SNPs contributed to promoter strength in a highly interactive and non-additive fashion, haplotype partitioning was successful in identifying six SNPs as major determinants of GH1 gene expression. The prediction and functional testing of hitherto unobserved super-maximal and sub-minimal promoter haplotypes was then used to test the efficacy of the haplotype partitioning approach. Electrophoretic mobility shift assays demonstrated that five SNP sites exhibit allele-specific protein binding. An association was noted between adult height and the mean in vitro expression value corresponding to an individual's GH1 promoter haplotype combination (p=0.028) although only 3.3% of the variance of adult height was found to be explicable by reference to this parameter. Three additional SNPs, identified within sites I and II of the upstream locus control region (LCR), were ascribed to three distinct LCR haplotypes. A series of LCR-GH1 proximal promoter constructs were used to demonstrate that 1) the LCR enhanced proximal promoter activity by up to 2.8-fold depending upon proximal promoter haplotype, and that 2) the activity of a given proximal promoter haplotype was also differentially enhanced by different LCR haplotypes. The genetic basis of inter-individual differences in GH1 gene expression thus appears to be extremely complex.     

用分子克隆技术构建D12S391基因座等位基因分型标准物及群体遗传学研究

目的 解决长期困扰短串联重复序列（short tandem repeat,STR）分型上存在的准确性和标准化问题。方法 先用PCR扩增出D12S391基因座的9个等位基因片段，将其插入pUC重组质粒中，经DNA测序分析证实插入片段的结构及大小，用国际标准将插入的等位基因片段进行命名，最后经转染、扩大培养、扩增及再鉴定后，制备出标准的D12S391等位基因分型标准物。结果 应用此法制备出大量的D12S391基因座等位基因分型标准物，并将其用于调查该基因座在德国Mainz地区、日本Miyazaki地区及中国成都汉族、北京汉族、新疆维吾尔族和甘肃回族6个群体中的基因型分布频率。D12S391基因座在各群体中均有较高的多态性，其非父排除概念及个人识别能力分别为0.609-0.786和0.940-0.952。结论 该法制备的STR基因座等位基因分型标准物在法医科学实践中应用价值极高，D12S391基因座是一个非常适合于群体遗传学研究和法医科学应用的遗传标记。     

HLA class II haplotypes associated with pulmonary interstitial lesions of polymyositis/dermatomyositis in Japanese patients

To elucidate the immunogenetic background of idiopathic inflammatory myopathies (IIM) such as polymyositis (PM), dermatomyositis (DM) and any overlapping subsets, with other collagen vascular diseases, HLA class I antigens and class II alleles were determined and compared from individuals with various clinical and serological features of IIM, including pulmonary interstitial lesions (PI). Seventy-three Japanese patients with myositis (32 PM, 18 DM, 23 overlapped subsets) and 62 healthy unrelated controls were enrolled onto the study. Statistical differences between groups were determined by the Fisher's exact probability test. Serum fluorescent antinuclear antibody, rheumatoid factor (RF), anti-SS-A/Ro antibody, anti-Jo1 antibody and anti-U1 RNP antibody were examined using routine methods. PI was detected by chest X-ray and/or computed tomography. In patients with DM, the frequency of the HLA-DRB1*1302-DQA1*0102-DQB1*0604 haplotype was significantly higher than in the healthy controls (42.1% vs 17.7%), and in the patients with PM (42.1% vs 9.4%). Furthermore, the frequency of the HLA-DRB1*0405-DQA1*03-DQB1*0401 haplotype was higher in the PM patients with PI than in the controls (50.0% vs 17.7%), and PM without PI (50.0% vs 5.5%). These results suggest that in terms of HLA class II association, Japanese DM and PM, and PM with and without PI, belong to different clinical groups.     

Skeletal manifestations in Fryns syndrome

We report on a female baby with Fryns syndrome who died soon after birth. The patient had short limbs, coarse face, hypoplastic lungs, diaphragmatic hernia, and acral hypoplasia. Literature review disclosed varying degrees of skeletal manifestations in Fryns syndrome; short limbs may be a component of Fryns syndrome. © 1995 Wiley-Liss, Inc.