Molecular-cytogenetic detection of a deletion of 1p36.3.

Abstract

We report a deletion of lp36.3 in a child with microcephaly, mental retardation, broad forehead, deep set eyes, depressed nasal bridge, flat midface, relative prognathism, and abnormal ears. The phenotype is consistent with that described for partial monosomy We now report the results of analysing our sample with one more HVP from the terminal region of chromosome lp. We have detected a chromosomal deletion of lp that was not apparent on routine cytogenetic testing in a child with developmental delay and congenital anomalies. Further analysis with lp probes, reverse painting, and FISH with telomere specific cosmids suggests that the child has a pure monosomy of the terminal 5-7 megabases (Mb) of lp. Materials and methods DNA ANALYSISVenous blood samples were taken from the patient and both parents. Epstein-Barr virus transformed lymphoblast cultures were established (available on request to JF). DNA was extracted from cell lines and peripheral blood by standard procedures.3 Samples from both parents and the affected offspring were digested with an appropriate restriction endonuclease, electrophoresed through 0.8% agarose gels, transferred to nylon membranes, and hybridised to radioactively labelled probes.3 PROBES AND GENETIC MAPPING Minisatellites used in this report are listed in table 1 and were cloned using the approach previously described4 ' and unpublished procedures. The cosmid containing CEB 108 and the chromosome 1 cosmid for D1F101S2 are derived from the ICRF chromosome 1 cosmid library. All the others are derived from a commercial library.4The minisatellite loci have been genetically mapped by typing of 40 CEPH families and heterozygosity estimated from 80 CEPH parents. The sex average distance from the lp telomere is deduced from our unpublished data at two more distal minisatellite loci (D1F35S2 and D1F102S1) and computed using CRIMAP version 2.4. All genotyping data are available from CEPH database version 8.1

Neurodevelopmental profile of a new dysmorphic syndrome associated with submicroscopic partial deletion of 1p36.3

“…The first child has been previously reported (Giraudeau et al 1997) and the monosomy was shown to be due to a de novo truncation of one of the chromosome 1 homologues rather than a polymorphism inherited from one of the parents.…”

“…Therefore, in at least three of the children, this was a de novo truncation. Reverse chromosome painting and microsatellite and southern blot analyses were used to map the extent of the deletion in child 1 (Giraudeau et al 1997).…”

Development and Clinical Application of an Innovative Fluorescence in situ Hybridization Technique Which Detects Submicroscopic Rearrangements Involving Telomeres

“…To demonstrate the diagnostic potential of the innovative FISH technique, 4 test cases were selected for analysis: (1) a phenotypically and cytogenetically normal male; (2) a phenotypically and cytogene tically normal female; (3) an IMR male patient originally reported as cytogenetically normal, but known by Southern analysis to exhibit a de novo deletion of a hypervariable probe mapping to the p-arm tel omere of chromosome 1 [7], and (4) an IMR female originally reported as cytogenetically normal using conventional techniques, but shown by Flint et al [6] to have a deletion of subtelomeric 22q and a trisomy of subtelomeric 9q.…”

“…Cosmid, PI and PAC clones used in current studies the genome are enriched for rearrangements. We have recently shown that as many as 8% of idiopathic mental retardation (IMR) referrals possess submicroscopic rear rangements involving telomeres and the associated subtelomeric DNA [6,7], Thus, the development of a FISHbased technique capable of detecting all deletions, tripli cations and balanced translocation events involving tel omeres and subtelomeric regions would be a useful diag nostic tool.…”

Position effect of human telomeric repeats on replication timing

“…The only naturally occurring situations in humans wherein telomeric repeats are adjacent to unique sequences at chromosome ends are those that occur in individuals with truncated chromosome ends that have been repaired by the process of telomeric healing (14). Several examples have been reported of individuals in whom idiopathic mental retardation has been associated with such chromosome-end truncations and telomere healing (15)(16)(17).…”