A recognisable behavioural phenotype associated with terminal deletions of the short arm of chromosome 8

We report the clinical findings in 5 patients with a terminal deletion of the short arm of chromosome 8. Mild developmental delay was constantly present, in association with microcephaly in 4 of 5 patients. Facial anomalies were mild or absent. A congenital heart defect was present in 3 patients: an atrioventricular septal defect (AVSD) in 2 and an atrial septal defect type II (ASDII) with pulmonary stenosis in one. A highly similar pattern of behavioural difficulties was present in the 3 older children (8–11 years), with outbursts of aggressiveness and destructive behaviour. Follow-up in one patient showed that at the age of 16 years, these behavioural problems had largely disappeared. This observation suggests that in addition to mental retardation, microcephaly, congenital heart defect (typically AVSD), a terminal deletion of chromosome 8p may be associated with a characteristic behavioural phenotype during childhood. Am. J. Med. Genet. 74:515–520, 1997. © 1997 Wiley-Liss, Inc.     

No evidence of uniparental disomy 2, 6, 14, 16, 20, and 22 as a major cause of intrauterine growth retardation

Intrauterine growth retardation (IUGR) is defined as length and/or weight below the 10th percentile. Etiology and, consequently, long-term outcome are extremely heterogeneous with chromosomal abnormalities found in up to 7%. Recently, uniparental disomy (UPD), i.e. the inheritance of both homologues of one pair of chromosomes from only one parent, was found in an increasing number of children with IUGR. Particularly, UPD of chromosome 7 was found in up to 10% of patients with IUGR and/or a phenotype of primordial growth retardation or Silver-Russell syndrome (SRS), but also UPD of chromosomes 2, 6, 14, 16, 20, and 22 was reported in single cases with IUGR. To evaluate impact and relevance of UPD in children with IUGR we investigated 23 sporadic cases with IUGR subsequently diagnosed as primordial growth retardation (n = 13) or SRS (n = 10) by molecular methods for UPD of chromosomes 2, 6, 14, 16, 20, and 22. No instance of UPD was found. Inheritance of all chromosomes investigated was biparental in all cases. Therefore, we conclude that UPD of these chromosomes is not a major cause of IUGR.     

A variety of genetic mechanisms are associated with the Prader–Willi syndrome

An extensive set of chromosome 15 DNA polymorphisms and densitometric analysis with four markers mapping to the Prader–Willi chromosome region (PWCR) of chromosome 15 have been used to characterize a cohort of 30 subjects with classical Prader–Willi syndrome (PWS). Molecular analysis enabled the classification of the PWS subjects into four groups: (A) 18 subjects (60%) had deletions of paternal 15q11–13 involving a common set of DNA markers. Two subjects had differently sized deletions, one larger and one smaller than the other cases. (B) Eight (27%) had maternal uniparental disomy for chromosome 15. (C) One (3%) had a marker chromosome carrying an extra copy of the PWCR. The marker chromosome was demonstrated to be of paternal origin and the two intact chromosomes were maternally derived. This case represents an apparent exception to the generally held view that PWS is associated with an absence of paternally inherited gene(s) located in the PWCR. (D) The remaining three cases (10%) had none of the above abnormalities. This last subgroup of patients has not previously been well characterized but could represent limited deletions not detectable with the markers used or abnormalities in the imprinting process. These cases represent potentially valuable resources to elucidate more precisely the fundamental disorders responsible for PWS. © 1994 Wiley-Liss, Inc.     

Ring chromosome 5 associated with severe growth retardation as the sole major physical abnormality

We report on a case of ring chromosome 5 in a 36-month-old girl with severe growth retardation, clinodactyly, mild psychological abnormalities, and normal facial appearance. Endocrine tests showed partial growth hormone deficiency. Cytogenetic investigation failed to demonstrate any apparent microscopic deletion of either short or long arm of chromosome 5 as consequence of ring formation. In 12% of cells examined, the ring was either absent or present in multiple copies. Only 3 previous cases of ring chromosome 5 have been reported in association with short stature of prenatal onset and minor anomalies, without mental retardation. © 1994 Wiley-Liss, Inc.     

29例伴del(20q)骨髓增生异常综合征的细胞遗传学和临床特征

目的 分析伴del(20q)的骨髓增生异常综合征(myelodysplastic syndrome，MDS)患者的细胞遗传学和临床特征。方法 对29例伴del(20q)MDS的细胞遗传学改变、临床表现、实验室检查特点及病程转归进行总结分析。结果 (1)29例del(20q)的MDS中，11例(37．9％)混合正常核型，难治性贫血(refractory anemia，RA)／伴环形铁粒幼细胞增多的难治性贫血(RA with ringed sideroblasts，RAS)组有9例，而原始细胞增多的RA(RA with excess blasts，RAEB)／转变中的RAEB(RAEB in transformation，RAEB-T)组2例；RA／RAS组中缺失以del(20q)(q11)多见(63．2%)，而RAEB／RAEB-T组中以del(20q)(q12)多见(70．0％)；RA／RAS组的附加核型改变和复杂核型改变发生率为26．3％、5．3％，均低于RAEB／RAEB-T组的50．0％和30．0％；(2)伴del(20q)的MDS多表现为两系或3系血细胞减少，几乎全部患者有红系和粒系病态造血，而58．6%的患者有巨核细胞病态造血，13例(44．8％)患者为两系病态造血，14例(48．3％)患者为3系病态造血，另2例为单纯红系病态造血；62．5％患者的有核红细胞糖原染色阳性和中性粒细胞碱性磷酸酶积分减低；81．8％患者有淋巴细胞的免疫学标记表达；(3)2例患者转化为急性非淋巴细胞性白血病(acute nonlymphocytic leukemia，ANLL)M2a型。结论 del(20q)可能是血液肿瘤中一种早期和初步的细胞遗传学异常，伴del(20q)的MDS以两系和3系血细胞减少及病态造血常见，可表达淋巴细胞标记，随病情进展正常核型减少而附加和复杂核型增加。     

Interstitial deletion of the short arm of chromosome 4 in a boy with mild psychomotor retardation and dysmorphism

A 17-month-old boy is reported with 46,XY,del(4) (p15.2p15.32). He had mild psychomotor retardation and multiple minor anomalies, without growth retardation or microcephaly, which differs from the classical 4p--syndrome (Wolf-Hirschhorn syndrome). The activity of dihydropteridine reductase, a genetic marker for chromosome 4p15.3, was half that in a normal control.     

A further patient with the Pitt-Rogers-Danks syndrome of mental retardation, unusual face, and intrauterine growth retardation

A further case of a syndrome of pre- and postnatal growth retardation, characteristic face, and unusual palmar creases is described. This child also had hypoplasia of labia majora and minora, deafness, and head nodding. Apparently sporadic occurrence in this family does not rule out autosomal recessive inheritance of this syndrome first described by Pitt, Rogers, and Danks in 1984.     

Interstitial deletion of 8q21→22 associated with minor anomalies,congenital heart defect,and Dandy-Walker variant

We describe an infant with a deletion of 8q21→22 who had distinct clinical manifestations including minor facial anomalies, a congenital heart defect, a Dandy-Walker variant, and mild to moderate developmental delay. Her facial characteristics included small, wide-spaced eyes, asymmetric bilateral epicanthal folds, a broad nasal bridge, a “carp-shaped” mouth, micrognathia, and prominent, apparently low-set ears. Three other reports describe children with larger proximal deletions of 8q that include 8q21 and q22. These four children all have similar facial appearance. Of the others reported, one had a congenital heart defect and one had craniosynostosis. This case, in addition to the previously noted three cases, helps in delineating a recognizable syndrome. © 1995 Wiley-Liss, Inc.     

Distal 8p deletion (8)(p23.1): An easily missed chromosomal abnormality that may be associated with congenital heart defect and mental retardation

We describe the clinical manifestations and molecular cytogenetic analyses of three patients with a similar distal deletion of chromosome 8. Each child had mild developmental delay and subtle minor anomalies. Two had cardiac anomalies but no other major congenital anomalies were present. High resolution G and R banding showed in all three patients del(8)(p23.1), but the breakpoint in case 1 was distal to 8p23.1, in case 2 was in the middle of 8p23.1, and in case 3 proximal to 8p23.1. Fluorescence in situ hybridization (FISH) studies with a chromosome 8 paint probe confirmed that no other rearrangement had occurred. FISH with a chromosome 8-specific telomere probe indicated that two patients had terminal deletions. Chromosome analysis of the parents of case 1 and mother of case 2 were normal; the remaining parents were not available for study. Thirteen individual patients including the three in this study, and three relatives in one family with del(8)(p23.1), have been reported in the past 5 years. Major congenital anomalies, especially congenital heart defects, are most often associated with a breakpoint proximal to 8p23.1. Three patients were found within a 3-year period in this study and five cases were found within 4 years by another group, indicating that distal 8p deletion might be a relatively common chromosomal abnormality. This small deletion is easily overlooked (i.e., cases 1 and 2 were reported as normal at amniocentesis) and can be associated with few or no major congenital anomalies. © 1996 Wiley-Liss, Inc.     

Interstitial deletions of the short arm of chromosome 4 in patients with a similar combination of multiple minor anomalies and mental retardation

Interstitial deletions of chromosome 4 have been described rarely and have had variable presentations. We describe the phenotypic characteristics associated with interstitial deletion of the p14–16 region of chromosome 4 in 7 patients with multiple minor anomalies in common, and with mental retardation. A review of published cases of interstitial deletions of the short arm of chromosome 4 is provided. These deletions present a distinct phenotype which is different from that of Wolf-Hirschhorn syndrome. © 1995 Wiley-Liss, Inc.     

Mental retardation in a boy with an interstitial deletion at Xp22.3 involving STS,KAL1, and OA1: Implication for the MRX locus

Although genotype-phenotype correlations in male patients with various types of nullisomy for Xp22.3 have assigned a locus for X-linked mental retardation (MRX) to an approximately 3-Mb region between DXS31 and STS, the precise location has not been determined. In this paper, we describe a 14 7/12 year old Japanese boy with mental retardation and an interstitial deletion at Xp22.3 involving STS, KAL1, and OA1, and compare the deletion map with that of previously reported three familial male patients with low-normal intelligence and a similar interstitial deletion at Xp22.3. The results suggest that the MRX gene is further localized to the roughly 1.5-Mb region between DXS1060 and DXS1139. © 1996 Wiley-Liss, Inc.     

Brief clinical report: A further patient with the Pitt-Rogers-Danks syndrome of mental retardation,unusual face,and intrauterine growth retardation

A further case of a syndrome of pre- and postnatal growth retardation, characteristic face, and unsual palmar creases is described. This child also had hypoplasia of labia majora and minora, deafness, and head nodding. Apparently sporadic occurrence in this family does not rule out autosomal recessive inheritance of this syndrome first described by Pitt, Rogers, and Danks in 1984.     

斑马鱼类胰岛素生长因子信号途径及作用机制研究进展

斑马鱼是研究早期发育中类胰岛素生长因子（insulin-like growth factors, IGF）信号途径的模式生物,斑马鱼IGF信号系统主要包括IGF配体、受体、结合蛋白（IGFBPs）。IGF配体包括IGF-1,IGF-2。受体为IGF-1R,该受体有两种全长结构（igf-1ra和igf-1rb）。结合蛋白包括IGFBP-1,IGFBP-2,IGFBP-3,IGFBP-5和 IGFBP-6,它们的结构特征已经阐明,从斑马鱼模式动物中获得的信息不仅可以为斑马鱼胚胎发育生物学提供新的观点,还可以进一步加深我们对一般意义上的脊椎动物的生长和发育的理解。本文就近年来斑马鱼IGF系统的进展作一综述。     

Blepharophimosis,ptosis, and epicanthus inversus syndrome (BPES) associated with interstitial deletion of band 3q22: Review and gene assignment to the interface of band 3q22.3 and 3q23

We report on a child with blepharophimosis, ptosis, and epicanthus inversus (BPES), developmental delay and an interstitial deletion of band q22 of chromosome 3. A review of chromosome 3q anomalies associated with eye abnormalities, specifically blepharophimosis and ptosis, strongly suggests that a locus for eyelid development is present at the interface of bands 3q22.3 and 3q23. © 1993 Wiley-Liss, Inc.     

15q26.3 deletions distal to IGF1R cause growth retardation,congenital heart defect and skeletal anomalies: Case report and review of literature

15q26 deletion is a rare genomic disorder characterized by intrauterine and postnatal growth retardation, microcephaly, intellectual disability, and congenital malformations. Here, we report a 4-month-old female with intrauterine growth retardation, short stature, pulmonary hypertension, atrial septal defect and congenital bowing of long bones of the legs. Chromosomal microarray analysis showed a de novo deletion of approximately 2.1 Mb at 15q26.3 region that does not include IGF1R. Our analysis of patients documented in the literature and the DECIPHER database with 15q26 deletions distal to IGF1R, including 10 patients with de novo pure deletions, allowed us to define the smallest region of overlap to 686 kb. This region includes ALDH1A3, LRRK1, CHSY1, SELENOS, SNRPA1, and PCSK6. We propose haploinsufficiency of one or more genes, besides IGF1R, within this region may contribute to the clinical findings in patients with 15q26.3 deletion.     

Interstitial deletion of 2q associated with craniosynostosis,ocular coloboma,and limb abnormalities: Cytogenetic and molecular investigation

We report on the clinical and cytogenetic findings in a 9-year-old boy with a de novo deletion of 2q, shown by molecular analysis to have arisen from the paternal chromosome. Examination of microsatellite markers indicated deletion of bands 2q24.3 and 2q31. Clinical findings included craniosynostosis, bilateral ocular colobomata, and limb abnormalities, the latter being an emerging association with deletion of this region of 2q. Am. J. Med. Genet. 70:324–327, 1997. © 1997 Wiley-Liss, Inc.