Partial trisomy 10q

Summary Five cases from two nonrelated families with partial trisomy 10q due to a reciprocal translocation t(10;17)(q25;p13) and t(10;11)(q24;q23), respectively, are reported. The phenotypic findings are compared with those of 17 previously published cases; the clinical data justify the conclusion that cases with trisomy 10q show a specific syndrome of mental retardation and malformation characterized by psychomotor retardation, growth retardation, hypotonia, high forehead, flat face, fine and arched eyebrows, antimongoloid slant of the eyes, narrow palpebral fissures, hypertelorism, short nose, bowshaped mouth, short neck, (kypho)scoliosis, and in some cases microcephaly.     

De novo 10q(q21q22) interstitial deletion

Summary We report a girl with a de novo interstitial deletion in the long arm of a chromosome 10. Clinical features are described.     

Distal trisomy 10q and limb defects

Analysis of the literature showed that hypoplasia (or aplasia) of tibiae was found at least in six persons with trisomy 10q25.2-qter. Therefore, these defects should be considered as a characteristic manifestation of the distal trisomy 10q. In most of these patients, tibial abnormalities were associated with other defects of the lower extremities (hypoplastic femora, ectrodactyly, preaxial polydactyly). Upper limbs were affected in one patient (as well as in her sib without tibial defects). Most likely, segment 10q25.2-qter contains a gene which (when triplicated) leads to maldevelopment of the limbs, and tibial malformations are only one manifestation of this field defect.     

Recurrent 10q22-q23 deletions: a genomic disorder on 10q associated with cognitive and behavioral abnormalities

Low-copy repeats (LCRs) are genomic features that affect chromosome stability and can produce disease-associated rearrangements. We describe members of three families with deletions in 10q22.3-q23.31, a region harboring a complex set of LCRs, and demonstrate that rearrangements in this region are associated with behavioral and neurodevelopmental abnormalities, including cognitive impairment, autism, hyperactivity, and possibly psychiatric disease. Fine mapping of the deletions in members of all three families by use of a custom 10q oligonucleotide array-based comparative genomic hybridization (NimbleGen) and polymerase chain reaction-based methods demonstrated a different deletion in each family. In one proband, the deletion breakpoints are associated with DNA fragments containing noncontiguous sequences of chromosome 10, whereas, in the other two families, the breakpoints are within paralogous LCRs, removing approximately 7.2 Mb and 32 genes. Our data provide evidence that the 10q22-q23 genomic region harbors one or more genes important for cognitive and behavioral development and that recurrent deletions affecting this interval define a novel genomic disorder.     

Partial trisomy 10q occurring in a family with a reciprocal translocation t(10;18)(q25;q23).

Partial trisomy 10q was observed in an eighteen year old girl with severe mental and physical retardation, microcephaly, a high forehead, microphthalmia, antimongoloid slants, low set ears and severely malformed extremities. A balanced translocation t(10q-;18q+), present in several family members, was identified by fluorescence and thermic denaturation techniques; the break points were 10q25 and 18q23. A comparison made with seven similar cases suggests a common, phenotypical appearance which may be of diagnostic value.     

Genomic analysis of human chromosome 10q and 4q telomeres suggests a common origin

The subtelomeric region of human chromosome 4q contains the locus for facioscapulohumeral muscular dystrophy (FSHD). The FSHD mutation is a deletion within an array of 3.3-kb tandem repeats (D4Z4). The disease mechanism is unknown but is postulated to involve position effect. A closely related 3.3-kb array on chromosome 10qter, in contrast, is not associated with a disease phenotype. We show here that the 4q homology on chromosome 10 is not confined to the 3.3-kb repeats but extends both proximally (42 kb) and distally to include the telomere. We have also identified the most distal expressed gene on 10q known so far, mapping only 96 kb from the 3.3-kb repeat array. A 4q variant has also been identified; there is 92%nucleotide identity between the two 4q forms, 4qA and 4qB. The 4qter and 10qter forms show homology to other chromosome ends, including 4p, 21q, and 22q, and these regions may represent a relatively common subtelomeric domain.     

Trisomie 10 partielle par translocation familiale t(1;10) (q44;q22)

Résumé Chez une enfant anormale, on observe un excès de matériel chromosomique sur la paire 1:1q+, et une translocation t(1q+;10q-) est dépistée dans la famille.L'analyse du caryotype après «dénaturation thermique ménagée» a permis d'individualiser le chromosome C anormal (10q-), de définir l'emplacement exact des points de cassure et de lier essentiellement l'état pathologique du patient à une trisomie partielle du bras long du chromosome 10.Cette trisomie se traduit principalement par une arriération mentale, une hypotrophie, des anomalies oculaires, une fente palatine, une mal-implantation des oreilles, un micrognathisme, des anomalies du squelette et une cardiopathie.

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Partial trisomy 10 due to hereditary translocation t(1;10) (q44;q22)

Summary A chromosome 1q+was observed in an abnormal girl. A balanced t(1q+;10q-) was found in the family.Application of a controlled thermic denaturation technique allowed recognition of the abnormal C as a 10q-and localization of the break points (1q44 and 10q22).The partial trisomy 10q of the proband had induced mental retardation, severe retardation of growth, ocular anomalies, agenesis of the palate, low implantation of the ears, micrognathia bone anomalies and cardiac malformation.

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Zusammenfassung Bei einem Mädchen mit Mißbildungen wurde ein Chromosom 1q+beobachtet. Eine balancierte t(1q+, 10q-) fand sich in der Familie.Die Identifikation des abnormen C als 10q- wurde durch Anwendung kontrollierter Wärmedenaturierung erreicht; auf diesem Wege wurden auch die Bruchpunkte identifiziert.Die partielle Trisomie 10q hatte bei dem Probanden einen geistigen Entwicklungsrückstand, eine schwere Wachstumsstörung, Augenanomalien, Fehlen des Gaumens, tief ansetzende Ohren, eine Mikrognathie, Knochenanomalien und eine Herzmißbildung zur Folge.

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Chargée de Recherche I.N.S.E.R.M. Chef de Service à l'Institut Pasteur de Lyon.

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Chargés de Recherche C.N.R.S.     

Two new cases of trisomy 10q21 to 10qter in two sisters due to paternal translocation t(9;10) (q34;q24)]

Two sisters with multiple congenital malformations were shown to be trisomic for 10q24 to 10qter as a consequence of malsegregation of the balanced paternal translocation t(9;10) (q34;q24). Comparison of their phenotype with that of other patients reported in the literature confirms the individuality of the partial 10q trisomy syndrome.     

Chromosome 4q;10q translocations; Comparison with different ethnic populations and FSHD patients

Background  

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by the weakness of facial, shoulder-girdle and upper arm muscles. Most patients with FSHD have fewer numbers of tandem repeated 3.3-kb KpnI units on chromosome 4q35. Chromosome 10q26 contains highly homologous KpnI repeats, and inter-chromosomal translocation has been reported.     

Partial trisomy 10q in three unrelated patients

This communication describes three unrelated patients with growth and psychomotor retardation, multiple congenital anomalies, and dysmorphic features who were found to have trisomies for the different long arm segments of chromosome 10. After reviewing the clinical and cytogenetic data from the literature and our three patients we concluded that: a) There are at least two different clinical syndromes associated with long arm trisomy of chromosome 10 only one of which, the well known 10q trisomy syndrome, is characterized with specific clinical features. The only trisomic segment common in this latter group of patients with similar phenotype, yet with different trisomic segments, is the distal two bands, q25 and q26. Therefore the determinants for the well-delineated 10q trisomy syndrome seems to be located on the distal bands q25 and q26 and this syndrome would preferably be named "distal 10q trisomy syndrome". b) The patients with proximal and/or middle long arm segment trisomies of chromosome 10 are rare and they have yet undefined clinical features.     

Distal trisomy 10q/partial monosomy 14q: an unusual clinical picture

A case of twin boy with partial trisomy for the distal part of the long arm of chromosome 10 (10q24-->qter) and a concomitant monosomy 14(q32-->qter) is reported. The chromosomal abnormalities resulted from a paternal balanced translocation involving chromosomes 10 and 14. An additional clinical feature was observed, viz. hypoplastic lungs. The proband's phenotype was compared to previously reported patients with partial trisomy 10q or 14q deletion.     

Familial translocation t(10;21)(q22;q22)

Summary A family is described with a translocation t(10;21)(q22;q22) transmitted through three generations. This family was studied for the apparition of several miscarriages and two sisters with multiple malformations. Both children had a probably partial trisomy of chromosome 10 and a monosomy of chromosome 21 due to a maternal adjacent-2 meiotic segregation.     

Malformative syndrome associated with a ring 10 chromosome and a translocated 10q/19 chromosome

Summary A male newborn with a ring 10 chromosome is described. The distal part of the long arm of chromosome 10, deleted during ring formation (10q25), is translocated to the short arm of chromosome 19.     

Monosomy 10q26-qter and trisomy 11q13-qter as a result ofde novo unbalanced translocation

A male infant with partial monosomy 10 q and partial trisomy 11q as a result ofde novo unbalanced translocation between the long arms of chromosomes 10 and 11: der(10)t(10;11)(q26;q13) is described. He had craniofacial dysmorphy, congenital heart defects, urogenital and cerebral anomalies, and severe developmental delay. To the best of our knowledge, this is the first report of this combination of chromosomal abnormalities.     

Meiotic segregation of chromosomes 13 and 14 in sperm of heterozygous Robertsonian translocation der(13;14)(q10;q10) carriers

Meiotic segregation of chromosomes 13 and 14 was assessed by fluorescence in situ hybridization on sperm of five heterozygous carriers of the most frequent Robertsonian translocation der(13;14). Alternate segregation mode was predominant (mean 78.2 ± 5.7%). The prevalence of balanced sperm varied from 69.4 to 86.5%. Adjacent segregation mode was detected in 18.64 ± 4.90% of sperm; 3:0 mode was detected in 2.48 ± 1.20% of sperm. These results are informative for reproductive counseling of Robertsonian translocation der(13;14) carriers providing information for assessment of probability of receiving normal/balanced embryos in assisted reproduction cycles.     

Susceptibility genes for age-related maculopathy on chromosome 10q26

On the basis of genomewide linkage studies of families affected with age-related maculopathy (ARM), we previously identified a significant linkage peak on 10q26, which has been independently replicated by several groups. We performed a focused SNP genotyping study of our families and an additional control cohort. We identified a strong association signal overlying three genes, PLEKHA1, LOC387715, and PRSS11. All nonsynonymous SNPs in this critical region were genotyped, yielding a highly significant association (P < .00001) between PLEKHA1/LOC387715 and ARM. Although it is difficult to determine statistically which of these two genes is most important, SNPs in PLEKHA1 are more likely to account for the linkage signal in this region than are SNPs in LOC387715; thus, this gene and its alleles are implicated as an important risk factor for ARM. We also found weaker evidence supporting the possible involvement of the GRK5/RGS10 locus in ARM. These associations appear to be independent of the association of ARM with the Y402H allele of complement factor H, which has previously been reported as a major susceptibility factor for ARM. The combination of our analyses strongly implicates PLEKHA1/LOC387715 as primarily responsible for the evidence of linkage of ARM to the 10q26 locus and as a major contributor to ARM susceptibility. The association of either a single or a double copy of the high-risk allele within the PLEKHA1/LOC387715 locus accounts for an odds ratio of 5.0 (95% confidence interval 3.2-7.9) for ARM and a population attributable risk as high as 57%.