Molecular evidence for true isochromosome 21q

Summary In one family a duplicated 21q was shown to be a true isochromosome, which segregates from mosaic mother to non-mosaic child with full Down syndrome phenotype. Densitometric analysis of Southern blots, using probe pPW228C for the distal long arm of chromosome 21, indicated that the 21q duplication contains two copies of the allele detected by the probe. Maternal mosaic karyotype of 45,XX,-21/46,XX/46, XX,-21,+21i(21q) also suggested transverse mitotic centromere division as the origin of the 21q isochromosomes. Morphologic analysis of chromosome heteromorphisms strengthened this interpretation because the free 21 missing in the cell line with 45 chromosomes was also missing in cells with the isochromosome. In a second family the cytogenetic data also suggested transmission of an i(21q) from mosaic mother to nonmosaic Down syndrome child but molecular evidence did not prove identity of alleles in the duplicated chromosome 21.     

Trisomy 21 by mirror duplication 46,XX,psu dic(21)ter rea (21q21q) (author's transl)

"Mirror image" duplication of chromosome 21 -- 46,XX,pter dic(21)ter rea(21q21q) -- was observed in a patient with the complete phenotype of trisomy 21 and a ses-sesquialtère de la SOD1.     

18q部分单体患儿的细胞和分子遗传学研究

临床发现1例智力低下伴轻度发育迟缓的女性患儿,对患儿进行G显带高分辨染色体核型分析, 发现18q21→qter缺失, 经多色荧光原位杂交和双色荧光原位杂交证实, 确定其核型为46,XX,del(18)(pter→q21:),ish del(18)(D18Z1+, qter-)。用DNA多态性方法分析, 该患儿从18q22.1至18qter区域内至少有8.7 Mbp丢失, 有MBP基因和GALNR基因缺失。缺失的18号染色体源自父亲。患者的智力低下和生长发育迟缓是18q21→qter缺失的结果, 或许与MBP基因和GALNR基因的缺失有关。     

Interstitial deletion of the long arm of chromosome 2 in a polymalformed newborn-karyotype: 46,XX,del(2)(q21;q24)

Summary This report describes a polymalformed female newborn presenting an interstitial deletion of the long arms of chromosome 2. Karyotype: 46,XX,del(2)(q21 q24).     

Transmission of a t(13q22q) chromosome observed in three generations with segregation of the translocation D1-trisomy syndrome.

A case of an inherited type of D/G translocation D1-trisomy syndrome was described. A female proposita who had the clinical signs of D1-trisomy syndrome was found to have a chromosome complement of 46,XX,--G,+t(DqGq). examination of Q- and G-stained karyotypes revealed that the chromosomes involved in the translocation were members of Nos. 13 and 22, or t(13q22q) with breaks at p12 of both chromosomes. C-stained figures also showed a large heterochromatin block in its centromeric region. The t(13q22q) chromosome was transmitted from the paternal grandmother of the proposita through at least three generations.     

Centric fission of chromosome 7 with 47,XX,del(7)(pter----cen::q21----qter)+cen fr karyotype in a mother and proximal 7q deletion in two malformed newborns

In the present paper we report a characteristic pattern of external and internal malformations in two male siblings with proximal 7q interstitial deletion as the unbalanced product of a rearranged chromosome 7 in the mother with karyotype 47,XX,del(7)(pter----cen::q21----qter),+fr. The interstitial 7q deletion in the mother included centromeric fission, break at 7q21 and preservation of the proximal q arm fragment.     

Double autosomal aberration: trisomy 21 and familial reciprocal translocation t(10;12)(p14;q21)]

A child with the Down syndrome revealed besides a regular trisomy 21, an enlargment of the short arm of chromosome 10, and the deletion of the long arm of chromosome 12. The proband's mother, who was phenothypically normal woman, appeared to be a carrier of the reciprocal translocation, her karyotype being: 46, XX, rep (10;12) (10qter leads to leads to 10p14; 12q21 leads to 12qter; 12pter leads to 12q21 : 10p14 leads to 10pter). Hence, the proband had double chromosomal aberration 47, XX, +21, rcp (10; 12) (10qter leads to 10p14 : 12q21 leads to leads to 12qter; 12pter leads to 12q21 : 10p14 leads to 10pter) mat. There is no reason to relate hard manifistation of the Down syndrome with the detected translocation. The influence of the mathernal non-devision in the meiosis and the rise of the trisomy 21 is discussed. In the following pregnancies it is advisable to amniocentesis.     

Structural chromosome abnormalities in Down syndrome: a study of two families.

Two families were ascertained through a proband with Down syndrome and a structural rearrangement involving two chromosomes 21. It is suggested that in one patient the chromosome is an isochromosome formed by misdivision of the centromere of a maternal telocentric chromosome 21 and that in the other a Robertsonian translocation involving chromosome 21 was inherited from the mother, who is a 46,XX/46,XX, -21,+t(21q21q) mosaic. The origin of the mosaicism is discussed and considered to be likely to be the result of breakage and reunion at the chromatid, rather than the chromosome, level.     

46,XX/46,XX,r (2)(p25q37) mosaicism: clinical and cytogenetic studies.

A severely mentally retarded and physically handicapped girl is described who has 46,XX/46,XX,r(2)(p25q37) mosaicism. This is the first ring 2 chromosome to be described in Man. Studies of the behaviour of the ring showed that it was stable in diploid cells which had increased in frequency over a period of seven years, but unstable in tetraploid cells which were at a much higher frequency than in normal individuals. It is concluded that in some cases the phenotypic consequences of ring chromosome formation may be due more to their disturbing the regulation of cell division than to the loss of genetic material. Current models of ring chromosome behaviour do not account for the induction of tetraploidy.     

First small supernumerary ring chromosome carrying 10q euchromatin in a patient with mild phenotype characterized by molecular cytogenetic techniques and review of the literature

We report the identification and characterization of the first supernumerary ring chromosome 10 containing a considerable proportion of 10q euchromatin by microdissection and reverse painting in a female patient presenting with short stature. Fluorescence in situ hybridization studies showed that the marker chromosome originates from chromosome 10 and includes the euchromatic bands p11.2 and q11.2. The supernumerary marker chromosome 10 was found in 14% of the peripheral blood lymphocytes analyzed. This constitutional mosaic could be confirmed in oral mucosa cells as a second cell system (16%) by interphase FISH using an alphoid centromeric probe for chromosome 10. Parental karyotypes were normal, uniparental disomy for the normal chromosomes 10 could be excluded by microsatellite analysis. The karyotype of the patient detected in peripheral blood cells can be described as mos 47,XX,+mar.rev ish r(10)(p11.2q11.2)(wcp10+,cep10+)/46,XX.     

De novo satellited 21q associated with corpus callosum dysgenesis, colpocephaly, a concealed penis, congenital heart defects, and developmental delay

De novo satellited 21q associated with corpus callosum dysgenesis, colpocephaly, a concealed penis, congenital heart defects, and developmental delay: We present clinical and cytogenetic data on an infant with de novo satellited 21 q. A 3-month-old boy was found to have microcephaly, developmental delay, hypertelorism, down-slanting palpebral fissures, large low-set ears, a prominent nose, a broad philtrum, a concealed penis, interventricular septal defects, corpus callosum dysgenesis, colpocephaly, ventriculomegaly, and a de novo karyotype of 46,XY,21qs. Standard Ag-NOR staining and FISH studies confirmed a satellite and a deletion on the long arm of a chromosome 21. Quantitative-fluorescent polymerase chain reaction using the polymorphic small tandem repeat markers specific for chromosome 21 determined a maternal origin of the deletion and the breakpoint between D21S156 (21q22.1) (present) and D21S53 (21q22.3) (absent), centromeric to the known minimal holoprosencephaly critical region, D21S13-21qter. The present case provides evidence of the correlation of a distal region of chromosome 21 to the phenotypic effects of monosomy 21.     

Partial monosomy of the long arm of chromosome 16 in a malformed newborn: Karyotype 46,XX,del(16)(q21)

Summary A polymalformed newborn with partial monosomy for the long arm of chromosome 16 is presented. Karyotype 46,XX,del(16)(q21).     

Six cases of partial duplication-deficiency 21 syndrome: 21(dupq22delp23) due to maternal pericentric inversion: inv(21)(p12;q22). A family study

Six probands, apparently not related, with a minimal phenotype of Down's syndrome were investigated between 1970 and 1984 in our laboratory. We found in all of them an identical chromosomal abnormality 46,XX or XY,-21,+ der21(dupq22delp23). The der 21 was due to aneusomie de recombinaison, each mother having an abnormal chromosome 21: inv(21)(p12;q22). The fathers' caryotypes were normal. All parents were young and healthy. Pedigrees were established in order to find a relationship between these families. Four of our probands could be related. Familial investigations are still in progress for the last two cases; the ancestors being born in the same small geographical area (within 50 km2) we think that we shall be able to establish a relationship with the others families.     

Distal trisomy 14q

Summary Two cases of chromosome 14 rearrangements with partial duplication which occurred de novo were analyzed by Southern blot analysis using IGH, D14S1 and PI probes. In the first case, with a 46,XX,14p+ karyotype, our study confirms that the additional material on chromosome 14p+ results from a duplication of the 14q region containing the IGH, D14S1 and PI loci. In the second case, our study reveals only one 14q32 locus per chromosome 14 indicating that the extra material does not contain the 14q32 region. Our results demonstrate that molecular probes of the 14q32 region are valuable tools for the characterisation of chromosome 14 abnormalities appearing de novo.     

Partial trisomy and monosomy 21 in an infant with an unusual de novo 21/21 translocation

A 3-month-old boy with a 46,XY,--21,+t(21;21)(pter leads to q22.3::q22.3 leads to q11::p11 leads to pter) karyotype, implicating trisomy for the 21q11 leads to 21q22.2 segment and monosomy for the 21q22.3 sub-band, is described. Most of the clinical features corresponded to Down syndrome ; other signs such as large ears, prominent nasal bridge and retromicrognathia were interpreted as the expression of 21q22.3 monosomy. The abnormal monocentric chromosome had satellites and stalks on both ends as a result of a 21q;21q translocation followed by deletion of one centromere region. Despite similar stalk size and NOR-Ag positiveness a significantly higher association frequency of the centrometric end as compared to the acentric end was found. This observation suggests that the satellite association phenomenon is not exclusively NOR-dependent, but that the centromeric and/or p11 regions of acrocentrics also play an important role.     

A child with mosaicism for deletion (14)(q11.2q13)

In this case report we describe a child with a de novo deletion in the (q11.2q13) region of chromosome 14. The child presented with dysmorphic features - anophthalmia, microcephaly, and growth retardation. Cytogenetic studies showed mosaicism. The karyotype was 46,XX,del(14)(q11.2;q13) [16] /46,XX [9]. We compared the features observed in this child with that of others with the same deletion reported in scientific literature and found that this is the first report of a child mosaic for this deletion. It is also the first time it has been reported in association with anophthalmia.     

Inherited pericentric inversion of chromosome no. 2 with Robertsonian translocation (13q 14q) resulting in trisomy for chromosome 13q

This report includes a patient with an inherited pericentric inversion of chromosome No. 2 in addition to a Robertsonian translocation resulting in trisomy for chromosome 13q. The chromosomal constitution of the proband was 46,XX,inv(2) (pter leads to p11 : : q14 leads to p11 : : q14 leads to qter); t(13,14) (13qter leads to 13p11 : : 14q11 leads to 14qter). Sequential QFQ, RFA and GTG banding techniques were employed on the chromosomes of all family members. The chromosomal constitutions of the father and his first child were normal while the mother had an inversion of chromosome No. 2 [46,XX,inv(2) (pter leads to p11 : : q14 leads to p11 : : q14 leads to qter)]. The proband inherited this abnormal chromosome. In addition, she had a de novo Robertsonian translocation involving chromosomes 13q and 14q resulting in trisomy of chromosome 13q.     

Prenatal detection of an unstable ring 21 chromosome

Summary An unstable ring chromosome 21 detected through prenatal studies was associated at birth with an apparently normal male phenotype. At 14 months of age, examination indicated only minor developmental delay. The majority of cells examined from amniocyte, fibroblast, and lymphocyte cultures contained an asymmetrical dicentric ring 21 chromosome which was larger than a normal chromosome 21. This ring is presumed to be a duplication for most of chromosome 21 and a deletion of part of the terminal regions. The karyotype is described as mos45, XY,-21/46,XY,r(21)(p13q22.3). The child is monosomic for part of the sub-band 21q22.3 in every cell and trisomic for the remainder of the chromosome in most of his cells. The terminal deletion does not appear to have been severely detrimental to the phenotype and the effective trisomy present in many cells studies was insufficient to cause the Down syndrome.     

An unbalanced translocation 46,XX,+der(18)t(18;21)(q12.2;q11.2)mat,-21 associated with maternal isodisomy 18pter-->18q12.2

We report a patient with a 46,XX,+der(18)t(18;21)(q12.2;q11.2)mat,-21 karyotype, in whom the rarely seen adjacent-2 segregation (according to the predicted pachytene diagram model) as well as two cross-overs, resulted in maternal isodisomy 18pter-->18q12.2.