一例伴有t(1;18)(p31;p11)易位的骨髓增生异常综合征

目的报告一例伴有t(1；18)(p31；p11)的骨髓增生异常综合征(myelodysplastic syndrome，MDS)。方法骨髓细胞24h培养后按常规方法制备染色体，采用R显带技术进行染色体核型分析；以1号和18号整条染色体涂染探针对其进行染色体涂染检测。结果常规细胞遗传学方法和染色体涂染分析均证实该患者具有t(1；18)(p31；p11)克隆性染色体异常。结论t(1；18)(p31；p11)易位是一种罕见的再现性染色体核型异常，在MDS中属于首次报道。     

Alagille syndrome with de Novo del(20) (p 11.2)

We report on an Arab boy with Alagille syndrome and a de novo deletion of the short arm of chromosome 20 with a 46,XY, del(20)(p11.2) chromosome constitution. Other reported cases are briefly reviewed.     

A dup(17)(p11.2p11.2) detected by fluorescence in situ hybridization in a boy with Alport syndrome

We describe a de novo dup 17p11 in a boy with Alport syndrome, mild mental retardation, and minor anomalies. Combining classical and molecular cytogenetics analyses, the karyotype was defined as 46,XY.ish dup (17)(p11.2p11.2)(D17S29++,D17S379+). Alport syndrome is associated with mutations in the type IV alpha chain collagen gene, however, no known collagen-related gene is currently mapped to 17p11. Duplications involving 17p11.2 have been reported in Charcot-Marie-Tooth disease, Dejerine-Sottas syndrome, and in a few sporadic patients with mental retardation and minor anomalies, however, no significant clinical similarity was found among these cases and the propositus. Further studies may clarify the meaning of the association between Alport syndrome and duplications of DNA sequences mapped at 17p11.2. Am. J. Med. Genet. 82:183–186, 1999. © 1999 Wiley-Liss, Inc.     

A 47,X,+t(X;X)(p22.3;p22.3)del(X)(p11.23q11.2),Y Klinefelter Variant with Morbid Obesity

Klinefelter syndrome is the most common type of genetic cause of hypogonadism. This syndrome is characterized by the presence of 1 or more extra X chromosomes. Phenotype manifestations of this syndrome are small testes, fibrosis of the seminiferous tubules, inability to produce sperm, gynecomastia, tall stature, decrease of serum testosterone and increases of luteinizing hormone and follicle stimulating hormone. Most patients with Klinefelter syndrome are tall, with slender body compositions, and reports of obesity are rare. We report the case of a 35-yr-old man with hypogonadism and morbid obesity and diabetes mellitus. He had gynecomastia, small testes and penis, very sparse body hair and his body mass index was 44.85. He did not report experiencing broken voice and was able to have erections. We conducted a chromosome study. His genotype was 47,X,+t(X;X)(p22.3;p22.3)del(X)(p11.23q11.2). In this case, the patient was diagnosed as Klinefelter syndrome. He showed rare phenotypes like morbid obesity and average height and the phenotype may be caused by the karyotype and the excess number of X chromosome. Further studies of the relationship between chromosomes and phenotype are warranted.     

Recurrent Wiedemann-Beckwith syndrome with inversion of chromosome (11)(p11.2p15.5)

A baby with Wiedemann-Beckwith syndrome (WBS) and her phenotypically normal mother carried the same paracentric inversion, inv(11)(p11.2 15.5), in the short arm of chromosome 11. A fetus, sib of the affected baby, had the same inversion and ultrasound scan showed exomphalos. The maternal grandmother is clinically and cytogenetically normal. The pattern of affection in this family is consistent with the suggestion that WBS can be caused by lack of a maternally imprinted gene at 11p15.5, and that in this family the inversion disrupts that gene.     

骨髓增生异常综合征免疫异常的表型

本文探讨免疫异常表型对骨髓增生异常综合征 (MDS )分型诊断及鉴别诊断价值。选用多种单克隆抗体 ,用流式细胞测定分析仪 ,对 4 9例MDS、 5 0例良性血液病患者 (贫血、粒细胞减少症、血小板减少性紫癜、感染等 )的骨髓细胞免疫表型进行测定分析研究。结果MDS 89 3%以上有二系或三系免疫表型异常 ,其中CD7、CD19、CD13、CD14、CD33、CD34、HLA DR免疫标志变化最大 ,明显高于正常对照组 (P <0 0 1) ;髓系抗原表达明显增高 ,而且随MDS进展恶化 ,FAB亚型抗原表达出现规律性变化 ,RA→RAS→RAEB→向RAEB T转化 ,较早期髓系抗原表达 (如CD13、CD33)逐渐增加 ,而较晚期髓系抗原表达 (如CD15、CD14 )逐渐减少 ;同时伴淋系抗原表达逐渐减少 ;骨髓干细胞 /祖细胞表面抗原 (如CD34、HLA DR ) ,随着MDS恶化发展 ,有逐渐明显增加异常表现 ,而且CD34、HLA DR早期抗原表达增高者 ,常常预后较差 ,易于转化成白血病。结论MDS患者骨髓细胞免疫异常表型 ,有利于MDS诊断、分型诊断及鉴别诊断 ,并对治疗、预后判断有重要指导价值[1,2 ,5] 。     

16p11.2微缺失综合征的研究进展

16p11.2微缺失综合征是一类先天性基因缺失的疾病,其人群发生率约为万分之三.该综合征的临床表现包括自闭症、发育迟缓、智力低下、脊柱畸形等一系列神经精神发育疾病,患者间表型异质性明显,而其致病机制目前尚未明确.本文从16p11.2微缺失的类型、临床表型、致病机制、检测技术等方面综述其研究进展,以便更好地为16p11.2微缺失综合征的机制研究和临床诊治提供帮助.     

Childhood Apraxia of Speech (CAS) in two patients with 16p11.2 microdeletion syndrome

We report clinical findings that extend the phenotype of the ∼550 kb 16p11.2 microdeletion syndrome to include a rare, severe, and persistent pediatric speech sound disorder termed Childhood Apraxia of Speech (CAS). CAS is the speech disorder identified in a multigenerational pedigree (‘KE'') in which half of the members have a mutation in FOXP2 that co-segregates with CAS, oromotor apraxia, and low scores on a nonword repetition task. Each of the two patients in the current report completed a 2-h assessment protocol that provided information on their cognitive, language, speech, oral mechanism, motor, and developmental histories and performance. Their histories and standard scores on perceptual and acoustic speech tasks met clinical and research criteria for CAS. Array comparative genomic hybridization analyses identified deletions at chromosome 16p11.2 in each patient. These are the first reported cases with well-characterized CAS in the 16p11.2 syndrome literature and the first report of this microdeletion in CAS genetics research. We discuss implications of findings for issues in both literatures.     

Apparent Sotos syndrome (cerebral gigantism) in a child with trisomy 20p11.2‐p12.1 mosaicism

We report on a child with apparent Sotos syndrome (cerebral gigantism) and partial duplication of the short arm of chromosome 20 mosaicism. Trisomy 20p11.2‐p12.1 was diagnosed using cytogenetic and FISH studies. The somatostatin receptor 4 (SSTR4) gene is included in the duplicated segment. This suggests that a dosage effect of this gene might be related to some of the clinical findings observed in our patient. The present observation emphasizes the importance of chromosome analysis in patients with well‐delineated but sporadic conditions. Am. J. Med. Genet. 91:273–276, 2000. © 2000 Wiley‐Liss, Inc.     

17p11.2p12 triplication and del(17)q11.2q12 in a severely affected child with dup(17)p11.2p12 syndrome

Multiple congenital anomalies/mental retardation syndromes due to genomic rearrangements involving chromosome 17p11.2 include deletion resulting in Smith-Magenis syndrome and a reciprocal duplication of the same region resulting in the 17p11.2 duplication syndrome. We present the clinical and molecular analysis of an 8-year-old male with a dup(17p11.2p12) who was evaluated for unusual severity of the phenotype. Fluorescent in situ hybridization (FISH) analysis not only confirmed the 17p duplication but also identified an approximately 25% mosaicism for tetrasomy 17p11.2p12. Whole-genome array comparative genomic hybridization (aCGH) was performed to identify other genomic rearrangements possibly contributing to the severe phenotype and the unusual features in the patient. The 17p duplication was determined by FISH and aCGH to encompass approximately 7.5 Mb, from COX10 to KCNJ12. An approximately 830 Kb deletion of 17q11.2q12, including exon 1 of an amiloride-sensitive cation channel neuronal gene, ACCN1, was also identified by aCGH; breakpoints of the deletion were confirmed by FISH. Sequencing the non-deleted allele of ACCN1 did not show any mutations. Western analysis of human tissue-specific proteins revealed that ACCN1 is expressed not only in the brain as previously reported but also in all tissues examined, including heart, liver, kidneys, and spleen. The large-sized 17p11.2p12 duplication, partial triplication of the same region, and the 17q11.2q12 deletion create a complex chromosome 17 rearrangement that has not been previously identified. This is the first case of triplication reported for this chromosome. Our study emphasizes the utility of whole-genome analysis for known cases with deletion/duplication syndromes with unusual or severe phenotypes.     

Autism multiplex family with 16p11.2p12.2 microduplication syndrome in monozygotic twins and distal 16p11.2 deletion in their brother

The pericentromeric region of chromosome 16p is rich in segmental duplications that predispose to rearrangements through non-allelic homologous recombination. Several recurrent copy number variations have been described recently in chromosome 16p. 16p11.2 rearrangements (29.5-30.1 Mb) are associated with autism, intellectual disability (ID) and other neurodevelopmental disorders. Another recognizable but less common microdeletion syndrome in 16p11.2p12.2 (21.4 to 28.5-30.1 Mb) has been described in six individuals with ID, whereas apparently reciprocal duplications, studied by standard cytogenetic and fluorescence in situ hybridization techniques, have been reported in three patients with autism spectrum disorders. Here, we report a multiplex family with three boys affected with autism, including two monozygotic twins carrying a de novo 16p11.2p12.2 duplication of 8.95 Mb (21.28-30.23 Mb) characterized by single-nucleotide polymorphism array, encompassing both the 16p11.2 and 16p11.2p12.2 regions. The twins exhibited autism, severe ID, and dysmorphic features, including a triangular face, deep-set eyes, large and prominent nasal bridge, and tall, slender build. The eldest brother presented with autism, mild ID, early-onset obesity and normal craniofacial features, and carried a smaller, overlapping 16p11.2 microdeletion of 847 kb (28.40-29.25 Mb), inherited from his apparently healthy father. Recurrent deletions in this region encompassing the SH2B1 gene were recently reported in early-onset obesity and in individuals with neurodevelopmental disorders associated with phenotypic variability. We discuss the clinical and genetic implications of two different 16p chromosomal rearrangements in this family, and suggest that the 16p11.2 deletion in the father predisposed to the formation of the duplication in his twin children.     

Complete trisomy 17p syndrome in a girl with der(14)t(14;17)(p11.2;p11.2)

We report on an 8-year-old girl with near-complete trisomy 17p syndrome due to a de novo unbalanced t(14;17)(p11.2;p11.2). She has features consistent with the previously described cases with complete trisomy 17p, including pre- and post-natal growth retardation, motor and mental retardation, skeletal anomalies, clinodactyly of the 5th finger, hypertrichosis, as well as facial characteristics including microcephaly, receding forehead, ptosis, low-set malformed ears, smooth philtrum, high-arched palate, and a short broad neck. Fluorescence in situ hybridization showed that the breakpoints were p11.2 for both chromosome 14 and 17. Microsatellite analysis showed that the duplicated 17p was of paternal origin, and indicated that the breakpoint involving 17p11.2 is most likely located within the approximately 1-Mb segment from the centromere, and not involving the proximal Smith-Magenis syndrome (SMS) low copy repeat. We compare the clinical features of our patient with those previously reported to further delineate the phenotype of complete trisomy 17p syndrome.     

Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2)

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly, mental retardation (MCA/MR) syndrome associated with deletion of chromosome 17 band p11.2. As part of a multi-disciplinary clinical, cytogenetic, and molecular approach to SMS, detailed clinical studies including radiographic, neurologic, developmental, ophthalmologic, otolaryngologic, and audiologic evaluations were performed on 27 SMS patients. Significant findings include otolaryngologic abnormalities in 94%, eye abnormalities in 85%, sleep abnormalities (especially reduced REM sleep) in 75%, hearing impairment in 68% (approximately 65% conductive and 35% sensorineural), scoliosis in 65%, brain abnormalities (predominantly ventriculomegaly) in 52%, cardiac abnormalities in at least 37%, renal anomalies (especially duplication of the collecting system) in 35%, low thyroxine levels in 29%, low immunoglobulin levels in 23%, and forearm abnormalities in 16%. The measured IQ ranged between 20–78, most patients falling in the moderate range of mental retardation at 40–54, although several patients scored in the mild or borderline range. The frequency of these many abnormalities in SMS suggests that patients should be evaluated thoroughly for associated complications both at the time of diagnosis and at least annually thereafter. © 1996 Wiley-Liss, Inc.     

Mosaicism for deletion 17p11.2 in a boy with the Smith-Magenis syndrome

We describe a 14-year-old boy with physical and behavioral manifestations of the Smith-Magenis syndrome. Low level mosaicism (11%) for deletion 17p11.2 was found in peripheral blood lymphocytes. The deletion was also observed in 100% of metaphases examined from skin fibroblast cultures. We confirm that the Smith-Magenis syndrome is associated with a highly recognizable phenotype. Because evidence of the abnormal cell line may be minimal or absent in peripheral blood, fibroblast studies are indicated for patients in whom mosaicism for deletion 17p11.2 is suspected clinically. © 1993 Wiley-Liss, Inc.     

Alagille syndrome with interstitial 20p deletion derived from maternal ins(7;20)

We present a 6-year-old Chinese boy with Alagille syndrome and an interstitial 20p deletion, with a karyotype of 46,XY,der(20)dir ins(7;20)(q11.23;p11.23p12.2 or p12.2p13)mat. He had a peculiar face and suffered from congenital heart disease, growth retardation, severe cholestasis, hepatosplenomegaly, and impaired renal function. The karyotype of his mother showed a balanced translocation, 46,XX,dir ins(7;20)(q11.23;p11.23p12.2 or p12.2p13), and her phenotype was normal. His dead elder brother was highly suspected as another victim of Alagille syndrome. The findings in the present family suggested that if Alagille syndrome is a single gene defect, the putative gene responsible for the syndrome would not be located at the insertion breakpoints but located within the deletion extent. © 1996 John Wiley-Liss, Inc.     

Chromosome 22q11.2 deletion in a boy with Opitz (G/BBB) syndrome

This report is on a 14-month-old boy with manifestations of Opitz (G/BBB) syndrome in whom a 22q11.2 deletion was found. Deletion analysis was requested because of some findings in this patient reminiscent of velocardiofacial (VCF) syndrome. The extent of aspiration and of respiratory symptoms in this child is not usually seen in VCF syndrome. Opitz syndrome maps to at least two loci, one on Xp, the other on 22q11.2. © 1996 Wiley-Liss, Inc.     

Rubinstein-Taybi syndrome with de novo reciprocal translocation t(2;16) (p13.3; p13.3)

We describe a girl with typical Rubinstein-Taybi syndrome with apparently balanced reciprocal translocation between chromosome 2 and 16. The patient has a condition characterized by mental retardation, typical facial manifestations, broad thumbs and first toes. Cytogenetic studies of the patient showed a reciprocal translocation without visible deletion, karyotype: 46, XX, t(2;16) (p13.3; p13.3). Her parents had normal chromosomes. These results suggest that the locus of the gene for the Rubinstein-Taybi syndrome may be situated at 2p13.3 or 16p13.3.