Characterization of a heritable partial monosomy 18p by molecular and cytogenetic analysis

Rigola, M A; Plaja, Alberto; Mediano, C.; Miró, R.; Egozcue, J.; Fuster, Carme

doi:10.1002/ajmg.1584

Cited by 29 publications

(21 citation statements)

References 15 publications

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“…She and her child had a very similar phenotype, including mental retardation, short stature, and HPE microform. Familial transmission of the del(18p) syndrome not associated with the presence of an unbalanced translocation is rare and has only been reported previously in few cases, all of them with maternal transmission (Uchida et al, 1965;Velagaleti et al, 1996;Rigola et al, 2001;Tsukahara et al, 2001).…”

Section: Discussionmentioning

confidence: 94%

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Midline defects in deletion 18p syndrome: clinical and molecular characterization of three patients

Portnoı̈

Gruchy²,

Marlin³

et al. 2007

Clinical Dysmorphology

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The phenotype of monosomy 18p varies widely, the main clinical manifestations being mental and growth retardation, and craniofacial dysmorphism. Clinical features also include growth hormone (GH) deficiency, or holoprosencephaly (HPE). Haploinsufficiency for TGIF, mapped to 18p11.3, is not generally sufficient to cause HPE. To perform a genotype-phenotype correlation, and delineate the region involved in GH deficiency, we carried out a molecular characterization of the 18p deletions, in three patients with midline defects. Two unrelated children, a 7-month-old girl and a 2-month-old boy had del(18p) syndrome and GH deficiency. In addition, the boy had HPE. HPE genes, SHH, ZIC2, SIX3, and TGIF, were tested by denaturing high-performance liquid chromatography and quantitative multiplex of PCR short fluorescent fragments analyses. A deletion of TGIF was confirmed, without any associated mutation for the tested HPE genes, suggesting the role of other genetic or environmental factors. The third patient was his moderately retarded mother. A set of chromosome 18p-specific BACs clones was used as fluorescence in-situ hybridization probes to define the breakpoints. Recently, it was found that there seem to be a breakpoint cluster in the centromeric region at 18p11.1, which was not observed in our patients. The girl was found to have a deletion of 10.3 Mb, with a breakpoint in 18p11.22. The boy and his mother had a smaller deletion (8 Mb), with a breakpoint in 18p11.23. These findings suggest that the distal region on 18p is involved in the main clinical features, and GH deficiency, in 18p deletions.

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Section: Discussionmentioning

confidence: 94%

“…The majority of reported cases are de-novo deletions, or inherited unbalanced translocations (Schinzel, 2001). Familial transmission of the del(18p) syndrome is rare and has only been reported previously in a few cases (Rigola et al, 2001).…”

Section: Introductionmentioning

confidence: 98%

Midline defects in deletion 18p syndrome: clinical and molecular characterization of three patients

Portnoı̈

Gruchy²,

Marlin³

et al. 2007

Clinical Dysmorphology

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“…Most of the Barber 2000Overhauser et al 1986Hand et al 2000Mascarello et al 1991Reddy 1999Batanian et al 2001Pelly et al 1992Davis et al 1999Barber et al 1991Li et al 2002Couturier et al 1985Hand et al 2000Witt et al 1988Rigola et al 2001 Duplication 1p21-p31 1q11-q22* 1q42.11-q42.12* 3q25-q25* 3q28-q29 4q31.3-q33* 5q15-q21* 6q24. Zaslav et al 1993Chan et al 2002Bortotto et al 1990Fryburg et al 1994Millard et al 1998Maltby et al 1999Li et al 1998Barber 2000Chan et al 2003Engelen et al 2000Harada et al 2002Stumm et al 2002Di Giacomo et al 2004Saxe et al 2003Robin et al 1997Cook et al 1997Wolff et al 1991 recorded cases are presented in Table 1 (after Barber).…”

Section: Unbalanced Euchromatic Abnormalities (Ubcas) Deletionsmentioning

confidence: 99%

Chromosome abnormalities without phenotypic consequences

2007

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Some changes in chromosome morphology, detected during cytogenetic analysis, are not associated with clinical defects. Therefore a proper discrimination of harmless variants from true abnormalities, especially during prenatal diagnosis, is crucial to allow precise counseling. In this review we described chromosome variants and examples of chromosome anomalies that are considered to be unrelated to phenotypic consequences. The correlation between the presence of marker chromosomes and a risk of clinical signs is also discussed. Structural rearrangements of heterochromatic material, satellite polymorphism, or fragile sites, are well-known examples of common chromosome variation. However, the absence of clinical effects has also been reported in some cases of chromosome abnormalities concerning euchromatin. Such euchromatic anomalies were divided into 2 categories: unbalanced chromosome abnormalities (UBCAs), such as deletions or duplications, and euchromatic variants (EVs). Recently so-called molecular karyotyping, especially whole-genome screening by the use of high-resolution array-CGH technique, contributed to revealing a high number of previously unknown small genomic variations, which seem to be asymptomatic, as they are present in phenotypically normal individuals.

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“…In the 18p deletion, however, maternal and paternal origins seem to be equally common [Schaub et al, 2002]. Familial transmission of partial monosomy 18p is rare and has only been previously reported in five cases, all of them with maternal transmission [Uchida et al, 1995;Velagaleti et al, 1996;Tonk and Krishna, 1997;Rigola et al, 2001;Tsukahara et al, 2001]. No report of spontaneous abortions with monosomy 18p have been reported, which might indicate that the 18p-deletion results in viable offspring and raises the possibility of substantial risk for recurrence in affected subjects.…”

Section: Introductionmentioning

confidence: 96%

Clinical and molecular characterization of individuals with 18p deletion: A genotype–phenotype correlation

Wester

Bondeson

Edeby

et al. 2006

American J of Med Genetics Pt A

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The deletion 18p syndrome is one of the most common chromosome abnormalities. The medical problems are mental and postnatal growth retardation, and sometimes malformations of the heart and brain. The individuals have some typical features, which might be easy to overlook and which are: ptosis, strabismus, hypertelorism, broad flat nose, micrognathia, big and low set ears. The aims of present study were to clinically and molecularly characterize the syndrome further in seven subjects with de novo 18p deletions and to perform genotype-phenotype correlation. All seven subjects had terminal deletions and no interstitial deletion was observed with subtelomeric FISH analyses. To define the extent of the 18p deletions and the parental origin of the deletion microsatellite- and FISH analyses were performed on genomic DNA and on lymphoblastoid cell lines of the study participants. Totally 19 chromosomes, 18 specific polymorphic microsatellite markers, and 5 BAC clones were used. The results revealed that the deletions were located in the centromeric region at 18p11.1 in four of the seven subjects. In the remaining three the breakpoints were located distal to 18p11.1 (18p11.21-p11.22). Four of the individuals had a paternal and three a maternal origin of the deletion. Genotype-phenotype correlation of the seven subjects suggests a correlation between the extent of the deleted region and the mental development. All the four children with a deletion in the centromeric region at 18p11.1 had a mental retardation (MR). Two of the three children with a more distal breakpoint (distal 18p11.21) had a normal mental development and one had a border-line mental retardation. There might be a critical region for the mental retardation located between 18p11.1 and 18p11.21. The children with a breakpoint at 18p11.1 had all a broad face, which was observed in only one of those with a more distal breakpoint, otherwise no genotype-phenotype correlation of the features was observed.

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Characterization of a heritable partial monosomy 18p by molecular and cytogenetic analysis

Cited by 29 publications

References 15 publications

Midline defects in deletion 18p syndrome: clinical and molecular characterization of three patients

Midline defects in deletion 18p syndrome: clinical and molecular characterization of three patients

Chromosome abnormalities without phenotypic consequences

Clinical and molecular characterization of individuals with 18p deletion: A genotype–phenotype correlation

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