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

Abstract

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.

Towards mapping phenotypical traits in 18p− syndrome by array-based comparative genomic hybridisation and fluorescent in situ hybridisation

“…4 Mb of 18p 8 and that both traits were found in two patients with deletions larger than 10 Mb. 7 In summary, we present a first tentative genotypephenotype map for patients with an 18pÀ syndrome. This study contributes towards achieving more accurate phenotype predictions in patients with monosomy of 18p necessary for precise genetic counselling.…”

“…One of them had an associated partial trisomy 8 and three had rather large deletions which hampered the attribution of phenotypical traits to different regions of 18p. 7 Here, we report on four patients, two of which are sibs, with partial monosomies 18p of different sizes ranging from 1.6 to 13.8 Mb as demonstrated by breakpoint analyses. The molecular karyotypes detected were correlated with the patients' phenotypes obtained by thorough clinical investigations.…”

Genetic Counselling in a Familial Deletion 18p Syndrome

“…It is known that is a correlation between the breakpoints (critical region p11.1 -p11.21) and the degree of learning difficulties. It suggests that patients with a deletion distal to this point have normal intelligence or only very mild learning difficulties [5,6]. If the breakpoints involve the distal half of 18p the child has post-natal growth retardation and seizures.…”

“…If the breakpoints involve the distal half of 18p the child has post-natal growth retardation and seizures. Ptosis and short neck have been mapped to the proximal half of 18p [6,7].…”

Síndrome por deleción 18p diagnosticado por hibridación genómica comparada. Presentación de un caso con fenotipo leve

“…7 Pacientes con deleciones más grandes cercanas a la región centromérica tienden a tener mayor discapacidad motora y déficit cognitivo, y trastornos psiquiátricos, faciales y malformaciones cerebrales graves. [8][9][10] Aunque el diagnóstico se realizó y fue suficiente con cariotipo convencional, el uso de array CGH, en este caso, permitió evaluar los genes involucrados en la zona delecionada.…”