Cytogenetic and molecular characterization of a de novo 4q24qter duplication and correlation to the associated phenotype

Abstract

We report on a newborn with severe psychomotor retardation, minor anomalies, congenital heart defects, thumb and urogenital abnormalities. Cytogenetic analysis showed a 4q24qter duplication, never described before, as the result of a de novo t(4;14). The extension of the duplicated 4q region was defined by FISH using YAC probes. The breakpoint was localized between 106.3cM (YAC 800f2, D4S1572) and 111 cM (YAC 744e4, D4S1564). Comparing our patient with those previously reported in literature, we observed some features mature frequently reported in these patients: psychomotor retardation, retromicrognathia, low set and/or malformed ears and some more specific traits: congenital cardiac defects, hypoplastic thumb and urogenital abnormalities.

‘Pure’ Partial Trisomy 4q26→q35.2 Resulting from a Familial Unbalanced Translocation t(4;10)(q26;q26.3)

“…Although our patient had partial trisomy 4q26 ] q35.2 and partial monosomy 10q26.3, her abnormal phenotypes may only ascribe to partial trisomy 4q26 ] q35.2. Compared to reported cases [Rinaldi et al, 2003;Lin et al, 2004;Battaglia et al, 2005;Cernakova et al, 2006], our patient had most of the described features of pure distal trisomy 4q syndrome, including mental retardation, growth retardation, microcephaly, language handicap, specific facies and thumb anomalies. Therefore, our patient may be regarded as a pure trisomy 4q case and benefit by delineating genotype-phenotype correlation.…”

“…Thus, the relationship between the phenotypes and the parts of duplicated segments has not yet been well defined [Battaglia et al, 2005]. Pure partial trisomy 4q, particularly if studied by molecular cytogenetic techniques, may be very useful to better define the correlation between genotype and phenotype and to understand the roles of some specific chromosomal regions [Rinaldi et al, 2003]. Although our patient had partial trisomy 4q26 ] q35.2 and partial monosomy 10q26.3, her abnormal phenotypes may only ascribe to partial trisomy 4q26 ] q35.2.…”

Partial trisomy 4q and preaxial limb defects

“…In that case, segment 4q31 will be the best candidate for harboring a gene, involved in the development of preaxial structures. Rinaldi et al [2003] 4q24qter Hypoplastic right thumb Dutrillaux et al [1975] 4q25q34 Absent right thumb, hypoplastic left thumb Todoroki et al [2001] 4q25q35 Hypoplastic thumb Cervenka et al [1976] 4q25qter Digitalization of thumbs Andrle et al [1979] 4q25qter Hypoplastic right thumb Najafzadeh et al [1983] 4q25qter Absent thumbs Concolino et al [1992] 4q25qter Triphalangeal thumbs Angle et al [2002] 4q25qter Hypoplastic right thumb Werner et al [2004] 4q27q28.2 Hypoplastic thumbs Lundin et al [2002] 4q27qter Finger-like thumbs Battaglia et al [2005] 4q28.3qter Absent right thumb, hypoplastic left thumb B. Preaxial polydactyly (PP) Biederman and Bowen [1976] 4q21qter PP of the right hand Xu et al [1982] 4q25qter PP of hands Frints et al [1996] 4q26q32 PP of the right hand Genčik et al [1982] 4q31qter…”

Familial 25.3 Mb inverted duplication of bands q32.1 to q35.1 on chromosome 4 with psychomotor impairments

“…Clinical heterogeneity of partial 4q trisomy has been reported, possibly due to the variability of the 4q duplicated segment and its accompanied anomalies. Pure duplications of 4q without a concurrent deletion are infrequent and have been described in fewer than 25 patients [Celle et al, 2000;Rinaldi et al, 2003;Lin et al, 2004;Otsuka et al, 2005;Egritas et al, 2010]. Here we present a three-generation family with pure 4q32.1-q35.1 duplication, never described before (Fig.…”