Partial trisomy 5q and partial monosomy 5q within the same family

The observation of partial trisomy for 5q31-5qter and partial monosomy for the same segment in two offspring within the same family is presented. Their normal mother was a balanced carrier of a reciprocal translocation 46,XX,t(5;10) (q31.3;q26). The trisomic female had craniofacial dysplasia, a short neck, clinodactyly of the 5th fingers, a small umbilical hernia, arhinencephalia, cerebellar hypoplasia, atrial septal defect, an accessory spleen, bifid uterus and vagina, hypoplastic ovaries. Potter syndrome with cystic dysplasia of the left kidney and agenesis of the right, urethral atresia, uterus unicornus with utero-urethral fistula, true hermaphroditism with two ovaries and one testicle were found in her stillborn sister. Analysis of the manifestations of monosomy 5q and trisomy 5q in the same family supports a well known fact that the effects of deletions are more pronounced than those of duplications for the same segments.     

Familial t(11;13)(q21;q14) and the duplication 11q, 13q phenotype

Cases of duplication of distal 11q or proximal 13q have been reported independently. A specific translocation resulting in duplication of distal 11q, [der(22)t(11;22)(q23;q11)], has been documented in over 40 cases. We report on a male fetus with chromosomal excess of both distal 11q and proximal 13q resulting from a familial translocation. This case supports the causal association of duplication 11q with neural tube defects. © 1993 Wiley-Liss, Inc.     

Evidence for a critical region for penoscrotal inversion,hypospadias, and imperforate anus within chromosomal region 13q32.2q34

Two unrelated patients with small distal deletions of the long arm of chromosome 13 are described, with shawl scrotum and penoscrotal transposition, penoscrotal hypospadias, a reduced perineum, and anal atresia. The patients have small deletions of 13(q32.2qter) and 13(q32q34), respectively. This report and the literature present evidence for one or possibly more gene(s) within region 13q32.2q34 which regulate the development of the ano-genital structures. The clinical spectrum includes bifid or shawl scrotum, hypospadias, biseptate uterus, malplaced and imperforate anus, and common cloaca. © 1996 Wiley-Liss, Inc.     

Neuroblastoma in a boy with MCA/MR syndrome,deletion 11q,and duplication 12q

Deletion 11q23→qter and duplication 12q23→qter are described in a boy with neuroblastoma, multiple congenital anomalies, and mental retardation. The patient has clinical manifestations of 11q deletion and 12q duplication syndromes. The possible involvement of the segment 11q23→24 in the cause of the neuroblastoma is discussed. © 1995 Wiley-Liss, Inc.     

15q24.1 BP4-BP1 microdeletion unmasking paternally inherited functional polymorphisms combined with distal 15q24.2q24.3 duplication in a patient with epilepsy,psychomotor delay,overweight, ventricular arrhythmia

15q24 microdeletion and microduplication syndromes are genetic disorders caused by non-allelic homologous recombination between low-copy repeats (LCRs) in the 15q24 chromosome region. Individuals with 15q24 microdeletion and microduplication syndromes share a common 1.2 Mb critical interval, spanning from LCR15q24B to LCR15q24C. Patients with 15q24 microdeletion syndrome exhibit distinct dysmorphic features, microcephaly, variable developmental delay, multiples congenital anomalies while individuals with reciprocal 15q24 microduplication syndrome show mild developmental delay, facial dysmorphism associated with skeletal and genital abnormalities. We report the first case of a 10 year-old girl presenting mild developmental delay, psychomotor retardation, epilepsy, ventricular arrhythmia, overweight and idiopathic central precocious puberty. 180K array-CGH analysis identified a 1.38 Mb heterozygous interstitial 15q24.1 BP4-BP1 microdeletion including HCN4 combined with a concomitant 2.6 Mb heterozygous distal 15q24.2q24.3 microduplication. FISH analysis showed that both deletion and duplication occurred de novo in the proband. Of note, both copy number imbalances did not involve the 1.2 Mb minimal deletion/duplication critical interval of the 15q24.1q24.2 chromosome region (74.3–75.5 Mb). Sequencing of candidate genes for epilepsy and obesity showed that the proband was hemizygous for paternal A-at risk allele of BBS4 rs7178130 and NPTN rs7171755 predisposing to obesity, epilepsy and intellectual deficits. Our study highlights the complex interaction of functional polymorphisms and/or genetic variants leading to variable clinical manifestations in patients with submicroscopic chromosomal aberrations.     

Two cases of 16q12.1q21 deletions and refinement of the critical region

Interstitial deletions of 16q chromosome including 16q12.1q21 region are very rare, with only three cases reported to date. Main clinical features include dysmorphisms, short stature, microcephaly, eye abnormalities, epilepsy, development delay, intellectual disability, and autism spectrum disorder.We report two independent subjects with 16q12.1q21 deletion syndrome presenting with dysmorphic facial features, developmental delay, strabismus, and aggressive behavior. A minimal region of overlap spanning 1.7 Mb on chromosome 16, including IRX5, GNAO1, and NUDT21 genes was shared among these two cases and those previously reported. This minimal region of overlap suggests the potential pathogenic role of these genes, previously implicated in diseases of the central nervous system.     

A 15q24 microduplication, reciprocal to the recently described 15q24 microdeletion, in a boy sharing clinical features with 15q24 microdeletion syndrome patients

A 15q24 microduplication, reciprocal to the minimal critical region for the recently described 15q24 microdeletion syndrome, was found in a 2-year-old boy by 244k Agilent oligoarray CGH analysis. The boy had global developmental delay and dysmorphic facial features, digital and genital abnormalities. The duplication was inherited from a healthy father, but was considered clinically significant, as the patient shared clinical features with 15q24 microdeletion syndrome patients. To our knowledge this is the first report of a patient with a 15q24 microduplication.     

Familial translocation t(10;14) (q26.1;q32.3): report of three offspring with 10q deletion and 14q duplication

We describe two brothers and a cousin with common clinical features, including mild mental retardation, motor delays, hypotonia with truncal ataxia, esotropia, and mild facial and hand dysmorphia. The initial routine chromosome study failed to detect any abnormality in the proband. Based on a high index of clinical suspicion, high-resolution chromosome studies were performed on the proband's parents. A small reciprocal translocation t(10;14) (q26.1;q32.3) was detected in the father. The breakpoint on the derivative chromosome 14 was further placed telomeric to the immunoglobulin heavy-chain gene cluster at the band q32.33 by fluorescence in situ hybridization. Studies of the proband and two affected paternal cousins revealed that each had inherited the same derivative chromosome 10 from their carrier parents. This unbalanced karyotype resulted from an adjacent-1 segregation of the 10;14 translocation.     

Molecular cytogenetic studies of duplication 9q32→q34.3 inserted into 9q13

Fluorescence in situ hybridization (FISH) studies using whole chromosome 9 painting probe, classical satellite (9q12-specific) probe and abl cosmid probe (locus: 9q34) were performed on a female infant who was born with multiple congenital anomalies and the karyotype 46,XX, 9q+. The results of FISH confirm the euchromatic nature of the extra material on the long arm of chromosome 9, and provide evidence that it is of chromosome 9 origin. The structural rearrangement has probably resulted from an insertion of a duplicated segment 9q32→q34.3 into band q13, as shown by the abl cosmid probe. The clinical features in this patient are similar to the previously reported cases of partial trisomy 9q3.     

Isochromosome 18q with karyotype 46, XX, i(18q). Cytogenetics and pathology

Cytogenetic and morphological findings of a 20-gestational-week-old female fetus with karyotype 46,XX,i(18q) are reported. The fetus displayed clinical features resembling Edward's syndrome. No characteristic symptoms of monosomy 18p could be observed.     

Boy with an interstitial 1q (q31q41) duplication confirmed by fluorescent in situ hybridisation

A 20-year-old man with multiple anomalies caused by a de novo duplication of the long arm of chromosome 1 is presented. The patient suffers from severe mental retardation, epilepsy, bronchial stenosis, and minor anomalies (e.g., hirsutism, midface dysplasia, and beaked nose). A G-banding analysis of the patient's chromosomes showed additional segments in chromosome 1. Fluorescent in situ hybridisation analysis with a chromosome 1 painting probe showed that the extra material originated from chromosome 1. Further analysis with cosmid probes demonstrated that the region involving chromosome bands 1q31 to q41 is present in a tandem duplication. Am. J. Med. Genet. 80:163–168, 1998. © 1998 Wiley-Liss, Inc.     

Segregation of a familial balanced (12;10) insertion resulting in dup(10)(q21.2q22.1) and del(10)(q21.2q22.1) in first cousins

An interchromosomal insertion in 3 generations of a family was ascertained through two developmentally delayed first cousins. Cytogenetic analysis using G-banding and chromosome painting showed an apparently balanced direct insertion of chromosome 10 material into chromosome 12, ins(12;10)(q15;q21.2q22.1), in the mothers and grandfather of these children. The proposita inherited only the derivative 10 chromosome, resulting in deletion of 10q21.2 → 22.1 while her cousin inherited only the derivative 12, resulting in duplication of 10q21.2 → 22.1. A comparison of the proposita with published deletion cases suggests a pattern of anomalies attributable to deletion of the 10q21 → q22 region: developmental delay, hypotonia, a heart murmur, telecanthus, broad nasal root and ear abnormalities. This is the first report of a nontandem duplication of the 10q21 → q22 region. The phenotype of the cousin with the duplication does not overlap greatly with published tandem 10q duplications. Finally, this report reaffirms the importance of obtaining family studies of patients with interstitial chromosomal abnormalities. Am J. Med. Genet. 69:188–193, 1997. © 1997 Wiley-Liss, Inc.     

Interstitial deletion of chromosome 5 in a neonate due to maternal insertion,ins(8;5)(p23;q33q35)

We describe an infant girl with an interstitial deletion of chromosome bands 5q33 to 5q35 inherited from a maternal interchromosomal insertion ins(8;5)(p23;q33q35) which was demonstrated by fluorescent in situ hybridization with whole chromosome paints. Physical anomalies included hypertonicity, microcephaly, short neck, apparently low-set ears, micrognathia, camptodactyly, mild rocker bottom feet, and hammer toe. Cardiac anomalies included a large ventricular septal defect, patent ductus arteriosus, pulmonary hypertension and hypoplastic right ventricle. She died at age 3 months. Am. J. Med. Genet. 86:289–293, 1999. © 1999 Wiley-Liss, Inc.     

Analysis of a 1‐megabase deletion in 15q22‐q23 in an autistic patient: Identification of candidate genes for autism and of homologous DNA segments in 15q22‐q23 and 15q11‐q13

We have identified a one megabase deletion in the 15q22‐15q23 region in a patient with autism, developmental delay, and mild dysmorphism. Genes that map within the deletion region and genes that are interrupted or rearranged at the deletion breakpoints are candidate genes for autism. Fluroescence in situ hybridization studies in this patient revealed that part or all of the PML gene is absent from one chromosome 15 and a BAC clone containing the D15S124 gene locus hybridizes to only one chromosome 15. BAC clones containing the PTPN9, and SLP‐1[hUNC24] genes showed markedly reduced hybridization in the 15q22‐q23 region on one chromosome 15 in the patient. These BACs also hybridize to the 15q11‐q13 region in close proximity to SNRPN and HERC2, and in this region there is equal intensity of signal on the normal and on the deleted chromosome. There are previous reports of deletions and duplications of the 15q11‐q13 region in patients with autism. Our patient represents the first report of a 15q22‐q23 deletion. Hybridization of the PTPN9 and Slp‐1 Bac clones to the 15q11‐q13 and the 15q22‐q23 regions of chromosome 15 may be due to the presence of PTPN9 or SLP‐1 gene sequences or to the presence of other gene sequences or to non‐coding homologous DNA sequences. The PTPN9 gene encodes a non‐receptor protein tyrosine phosphatase. The Slp‐1 [hUNC24] gene is expressed mainly in the brain. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:765–770, 2000. © 2000 Wiley‐Liss, Inc.     

16q22.1 microdeletion and anticipatory guidance

The widespread availability of comparative genomic hybridization (CGH) array analysis has led to the discovery of several genomic microdeletion‐associated syndromes and has identified possible genetic causes for patients with previously unexplained clinical features. We report the case of four unrelated patients who share common clinical characteristics, namely failure to thrive, developmental delay, dysmorphic features, and congenital anomalies. CGH array analysis revealed that all four patients had a de novo microdeletion at 16q22.1. In this case report, we describe the clinical features of these patients and offer possible explanations for how their 16q22.1 microdeletion may account for their symptoms. We also suggest guidelines for the management of 16q22.1 microdeletion based on the phenotypes seen in our patients and the function of the genes affected by this microdeletion.     

6.7 Mb interstitial duplication in chromosome band 11q24.2q25 associated with infertility, minor dysmorphic features and normal psychomotor development

We report on a healthy man with high normal intelligence, minor dysmorphic features and infertility due to hypogonadism and azoospermia. Cytogenetic analysis showed a 6.7 Mb duplication in chromosome band 11q24.2q25, which could be confirmed with FISH and molecular karyotyping using an Affymetrix GeneChip Human Mapping 250 K Nsp SNP array.     

Blepharophimosis,ptosis, epicanthus inversus syndrome,a new case associated with de novo balanced autosomal translocation [46,XY,t(3;7)(q23;q32)]

This paper reports a further case of blepharophimosis, ptosis, epicanthus inversus (BPES) syndrome associated with a reciprocal translocation [46,XY,t(3;7)(q23;q32)], involving band 3q23. This case supports the assignment of a BPES gene(s) to the 3q23 region. © 1994 Wiley-Liss, Inc.