Partial trisomy of the distal part of 10q: a report of two Egyptian cases

Partial trisomy of the distal third of the long arm of chromosome 10 is a well defined but rare syndrome. Most cases result from an unbalanced translocation. Growth retardation, developmental delay and characteristic dysmorphic features are well described in the syndrome. This report includes 2 Egyptian cases with partial 10q trisomy involving different breakpoints. Cases were subjected to full clinical examination and detailed cytogenetic analysis using conventional and FISH studies. Results showed that the karyotype of case 1 was 46,XX,der(7)t(7;10)(p22;q23).ish(wcp7+;wcpl0+) and the karyotype of case 2 was 46,XX,der(7)t(7;10)(p22;q25).ish(wcp7+;wcp 10+). The chromosomal abnormalities in case 1 resulted from a paternal balanced translocation while case 2 resulted from a maternal balanced translocation involving chromosomes 10 and 7 in both cases. The probands' phenotypes were correlated to the breakpoints and compared to previously reported cases with partial trisomy 10q. Both cases had the well characterized phenotype of the distal trisomy of 10q in the form of mental retardation, microcephaly, characteristic dysmorphic facies and limb anomalies as trisomy in both cases involved the 10q25-->qter region. However, case 1 with 10q23-->qter duplication showed more severe clinical manifestations than case 2 with less extensive 10q25-->qter trisomy. These included severe failure to thrive, cardiac involvement and death from respiratory and heart failure. This study confirmed that unbalanced chromosome regions of the long arm of chromosome 10 play an important role in developmental malformations and that a more severe form is associated with involvement of 10q23. It also emphasizes the importance of increasing public awareness regarding these chromosomal rearrangements and the importance of genetic counseling and prenatal diagnosis to avoid recurrences and associated family stress. This was clearly demonstrated in the second family in this study as the couple refused any follow up or further investigations due to religious beliefs despite their social and educational level.     

Distal symphalangism: a report of two families

This study describes distal symphalangism in 36 individuals in two families, one of which is the largest pedigree of this rare defect yet documented. Distal symphalangism is ankylosis or rigidity of the distal interphalangeal joints of the hands and/or feet. The findings of this report substantiate the mutation as an autosomal dominant phenotype. Several manifestations of distal symphalangism were observed, including the lack of cutaneous creases over affected joints, brachydactyly, fourth-finger hypophalangism, absent nails, and rudimentary nails. Variability ranged from just toes affected, to a single finger affected, to all fingers and all lesser toes affected. The most common expression of the mutant gene was rigid index fingers. Craniosynostosis, premature closure of the sutures of the skull, was encountered twice in the larger of the two families. It is a possible pleiotropic effect of distal symphalangism.     

Angelman syndrome: three molecular classes identified with chromosome 15q11q13-specific DNA markers

Angelman syndrome (AS) and Prader-Willi syndrome (PWS) share a cytogenetic deletion of chromosome 15q11q13. To determine the extent of deletion in AS we analyzed the DNA of 19 AS patients, including two sib pairs, with the following chromosome 15q11q13--specific DNA markers: D15S9-D15S13, D15S17, D15S18, and D15S24. Three molecular classes were identified. Class I showed a deletion of D15S9-D15S13 and D15S18; class II showed a deletion of D15S9-D15S13; and in class III, including both sib pairs, no deletion was detected. These molecular classes appear to be identical to those observed in PWS. High-resolution cytogenetic data were available on 16 of the patients, and complete concordance between the presence of a cytogenetic deletion and a molecular deletion was observed. No submicroscopic deletions were detected. DNA samples from the parents of 10 patients with either a class I or a class II deletion were available for study. In seven of the 10 families, RFLPs were informative as to the parental origin of the deletion. In all informative families, the deleted chromosome 15 was observed to be of maternal origin. This finding is in contrast to the paternal origin of the deletions in PWS and is currently the only molecular difference observed between the two syndromes.     

Mandibuloacral dysplasia: a report of two Egyptian cases

Mandibuloacral dysplasia (MAD) is a rare disorder. Only 35 patients, coming from 22 families, have been reported worldwide. We report on two Egyptian unrelated girls with MAD. The first patient presented at the age of 5 years with acral defect and partial alopecia. The second patient presented at the age of 17 years with progressive micrognathia and loss of subcutaneous fat from the limbs. Physical examination detected the craniofacial, skeletal and cutaneous changes characteristic of MAD. Both patients were short with progeroid facies and loss of subcutaneous fat from the extremities, which fits lipodystrophy type A pattern. Radiological examination revealed delayed closure of cranial sutures, hypoplastic mandible, hypoplastic clavicles, and acroosteolysis. Both patients had normal glucose tolerance, but had fasting and post-prandial hyperinsulinemia, suggestive of insulin resistance. One patient had elevated serum triglycerides and low normal cholesterol levels, while the other patient had normal levels. Serum leptin was normal in both patients. We review the literature on mandibuloacral dysplasia and discuss the differential diagnosis.     

11q Aneuploidy: Partial monosomy and trisomy in the children of a mother with a t(3;11)(p27;q23) translocation

Summary A woman with a balanced translocation t(3;11)(p27;q23) has had three abnormal children. The first child died in infancy, and of the two survivors who show segregation of the derivative maternal translocated chromosomes, one exhibits partial trisomy 11q and the other partial monosomy 11q. The two cases are compared with each other and with reported examples. Moreover, 11q break points are discussed.     

Duplication within chromosome region 15q11-q13 in a patient with similarities to Prader-Willi syndrome confirmed by region-specific and band-specific fish.

We report on a patient presenting with mental retardation and obesity and a proximal duplication of chromosome 15. The patient shared some clinical signs with Prader-Willi syndrome. With a region-specific paint, generated by microdissection, a duplication in region 15q11.2-q13 was shown to be present. Subsequently, FISH with probes localized to chromosome region 15q11.2-q12 and microsatellite analysis was used to characterize this chromosome aberration further and an insertion duplication within the region frequently deleted in Prader-Willi and Angelman syndrome was demonstrated.     

Familial congenital brachial palsy: a report of two affected Egyptian families

Congenital brachial palsy is still a relatively common birth defect and almost a sporadic disorder. This work presents 2 unrelated Egyptian families; had several members in successive generations with severe unilateral congenital brachial palsy. Pedigree analysis of both families and the high rate of consanguinity among them are highly suggestive of autosomal recessive inheritance with variable expression.     

Partial trisomy of distal 5q and partial monosomy of Xp as a result of mating between two translocation carriers: a female with a balanced translocation t(X;5)(p11;q31) and a male with a der(13;14)(q10;q10)--a case report and a family study

This paper presents the family of a dysmorphic child with the phenotypic features of Turner's syndrome and 5q trisomy, whose parents are both carriers of a balanced translocation. The parents' karyotypes are 46,X,t(X;5)(p11.1;q31) and 45,XY,der(13;14)(q10;q10), respectively.     

3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome

We report the identification of six patients with 3q29 microdeletion syndrome. The clinical phenotype is variable despite an almost identical deletion size. The phenotype includes mild-to-moderate mental retardation, with only slightly dysmorphic facial features that are similar in most patients: a long and narrow face, short philtrum, and high nasal bridge. Autism, gait ataxia, chest-wall deformity, and long and tapering fingers were noted in at least two of six patients. Additional features--including microcephaly, cleft lip and palate, horseshoe kidney and hypospadias, ligamentous laxity, recurrent middle ear infections, and abnormal pigmentation--were observed, but each feature was only found once, in a single patient. The microdeletion is approximately 1.5 Mb in length, with molecular boundaries mapping within the same or adjacent bacterial artificial chromosome (BAC) clones at either end of the deletion in all patients. The deletion encompasses 22 genes, including PAK2 and DLG1, which are autosomal homologues of two known X-linked mental retardation genes, PAK3 and DLG3. The presence of two nearly identical low-copy repeat sequences in BAC clones on each side of the deletion breakpoint suggests that nonallelic homologous recombination is the likely mechanism of disease causation in this syndrome.     

Clinical and molecular characterization of a combined 17p13.3 microdeletion with partial monosomy 21q21.3 in a 26-year-old man

We led a clinical and molecular characterization of a patient with mild mental delay and dysmorphic features initially referred for cytogenetic exploration of an azoospermia. We employed FISH and array CGH techniques for a better definition and refinement of a double chromosome aberration associating a 17p microdeletion with partial monosomy 21q due to 1:3 meiotic segregation of a maternal reciprocal translocation t(17;21)(p13.3;q21.2) revealed after banding analysis. Brain MRI depicted partial callosal and mild diffuse cerebral atrophies, but without expected signs of lissencephaly. The patient's karyotype formula was: 45,XY,der(17)t(17;21)(p13.3;q21.2)mat,-21. FISH study confirmed these rearrangements and array CGH analysis estimated the loss sizes to at least 635 kb on chromosome 17 and to 15.6 Mb on chromosome 21. The absence of lissencephaly and major brain malformations often associated with 17p terminal deletions could be attributed to the retention of PAFAH1B1, YWHAE and CRK genes. Dysmorphic features, moderate mental impairment and minor brain malformations could result from the 21q monosomy and particularly the partial deletion of the APP-SOD1 region. Azoospermia should result from gamete apoptosis induced by a control mechanism triggered in response to chromosome imbalances. Our study provides an additional case for better understanding and delineating both 17p and 21q deletions.     

Partial trisomy 7q and monosomy 13q in a child with disorder of sex development: Phenotypic and genotypic findings

Terminal 7q duplication and terminal 13q deletion are two conditions with variable phenotypes including microcephaly, thumb a-/hypoplasia, cortical dysplasia, microphtalmia, intellectual disability and dysmorphic features. We describe a boy born to a mother with a reciprocal t (7;13) who combines both a terminal 7q33-qter duplication and terminal 13q33-qter deletion through the inheritance of a derivative chromosome 13 (der (13)). The patient presented with developmental delay, facial and non-facial dysmorphic features, hypertonia, genital abnormality and skeletal malformation but no thumb a-/hypoplasia or microphtalmia. Knowing the exact breakpoints of his chromosomal aberrations using high resolution array CGH (aCGH) and comparison of his phenotypes with those of 24 and 59 previously published cases of 7q duplication and 13q deletion, respectively, allow us to further narrow the size of the proposed critical regions for microcephaly, thumb a-/hypoplasia and hypo/hypertonia on chromosome 13.     

Localisation of a gene for Papillon-Lefèvre syndrome to chromosome 11q14–q21 by homozygosity mapping

Papillon-Lefèvre syndrome is an autosomal recessively inherited palmoplantar keratoderma of unknown aetiology associated with severe periodontitis leading to premature loss of dentition. Three consanguineous families, two of Turkish and one of German origin, and three multiplex families, one of Ethiopian and two of German origin, with 11 affected and 6 unaffected siblings in all were studied. A targeted genome search was initially attempted to several candidate gene regions but failed to demonstrate linkage. Therefore a genome-wide linkage scan using a combination of homozygosity mapping and traditional linkage analysis was undertaken. Linkage was obtained with marker D11S937 with a maximum two-point lod score of Z _max = 6.1 at recombination fraction θ = 0.00 on chromosome 11q14–q21 near the metalloproteinase gene cluster. Multipoint likelihood calculations gave a maximum lod score of 7.35 between D11S901 and D11S1358. A 9.2-cM region homozygous by descent in the affected members of the three consanguineous families lies between markers D11S1989 and D11S4176 harbouring the as yet unknown Papillon-Lefèvre syndrome gene. Haplotype analyses in all the families studied support this localisation. This study has identified a further locus harbouring a gene for palmoplantar keratoderma and one possibly involved in periodontitis. Received: 19 July 1997 / Accepted: 22 August 1997     

Cytogenetic,FISH and DNA studies in 11 individuals from a family with two siblings with dup(21q) Down syndrome

A Spanish family has previously been described with two siblings with dup(21q) Down syndrome. The father has a normal karyotype. The mother has a microchromosome. Cytogenetic, fluorescence in situ hybridization and DNA studies have now been carried out on the family. Findings include that the mother has three different chromosome anomalies, viz. (1) a chromosome 22 with an unusual pericentromeric region that contains alphoid DNA from chromosomes 21/13 and chromosome 22, (2) an isochromosome 21p in the frequent cell line and (3) an isochromosome 21q in a rare second cell line. A possible explanation is that the mother developed from a zygote with trisomy 21 and that mitotic error in early development resulted in the formation of two cell lines with karyotypes of 47,XX,+i(21p) and 47,XX,+i(21q), respectively. The unusual chromosome 22 represents a hitherto undescribed chromosome anomaly and one possible explanation is a translocation of the short arms between chromosomes 21/13 and 22 in the ancestry of the family. The relationship between the unusual chromosome 22 and the isochromosome formation in the mother is not known. However, all three chromosome anomalies involve the alphoid DNA of chromosome 21/13, indicating that this is not a chance finding.     

Visualizing DNA domains and sequences by microscopy: a fifty-year history of molecular cytogenetics.

This short review presents a historical perspective of chromosome research during the last 50 years. It shows how molecular knowledge and technology of DNA entered cytogenetics step by step making it now daily practice in almost every modern chromosome lab. A crucial milestone in these decades has been the development of in situ protocols by Pardue and Gall, among others, initially only with isotopic labels, and without fluorescence microscopy and sophisticated detection systems. But these very first in situ hybridizations played a decisive role in the discovery of chromosome banding profiles, which were obtained under specific chemical, physical, or enzymatic conditions, thus effecting stainability of specific chromosome regions. In the decades thereafter, numerous technical improvements were achieved leading to complex multi-colour fluorescence in situ hybridization (FISH) protocols for mammals, plants, and insects. Highly improved detection systems of the FISH signals further allowed detection of DNA targets of up to 50 bp, whereas other protocols, which were developed to stretch chromatin fibres to the full length of native DNA, improved spatial resolution of adjacent targets in the light microscope to 1 kb.     

Translocation (14;21)(q11;q22) in a woman with history of abortions and a child with Down's syndrome

A translocation (14;21)(q11;q22) was observed in a woman with history of abortions and in her child with Down's syndrome. This appears to be the first report of such a translocation with no centric fusion between the acrocentric chromosomes leading to a count of 45 chromosomes in the carrier and giving birth to a Down's syndrome child.     

The 4p- syndrome,with a report of two new cases

Summary This report illustrates the typical clinical and cytogenetic findings in two children with the Wolf syndrome (4p- syndrome). The literature of previously published cases is reviewed.

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Zusammenfassung In diesem Bericht werden die typischen klinischen und cytogenetischen Befunde bei zwei Kindern mit Wolf-Syndrom (4p--Syndrom) dargestellt. Bei dieser Gelegen-heit wird eine Übersicht über die bisher publizierten Fälle gegeben.

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Supported by contract No. 20.122 F.W.G.O., Belgium

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Bevoegd Navorser N.F.W.O., Belgium