Duplication of (2)(q11.1‐q13.2) in a boy with mental retardation and cleft lip and palate: Another clefting gene locus on proximal 2q?

Abstract

A 4-year-old boy with left cleft lip and cleft palate, multiple minor anomalies and developmental delay revealed an abnormal chromosome 2 with enlarged proximal long arm, de novo, in his karyotype. Fluorescence in situ hybridization with a chromosome 2 library and band-specific YACs confined the duplicated segment to 2q11.1-q13.2 and indicated a direct tandem duplication due to unbalanced crossover between chromatids.

A new case of 2q duplication supports either a locus for orofacial clefting between markers D2S1897 and D2S2023 or a locus for cleft palate only on chromosome 2q13‐q21

“…There have been only nine previous reports on a total of 10 patients with a pure duplication or triplication of the proximal chromosome 2q [Wang and Hunter, 1979;Mu et al, 1984;Lanman et al, 1986;Grevengood et al, 1993;Cooke et al, 1995;Glass et al, 1998;Wang et al, 1999;Riegel and Schinzel, 2002;Wegner et al, 2004]. Due to the variable clinical features and chromosomal breakpoints, no common pattern of a proximal duplication 2q syndrome could be defined from these cases, not even from the patients in whom breakpoints presumably were very similar [Riegel and Schinzel, 2002]. However, a newborn recently described by Wegner et al [2004] had a relatively similar duplication of chromosome 2 (q13-q23) and clinical features similar to our case such as growth retardation, cleft palate, micrognathia, dysplastic ears, heart anomaly, and bilateral cryptorchidism.…”

“…Strong associations have been found between nonsyndromic CL/P and CPO and most if not all human chromosomes, including chromosome 2 [Brewer et al, 1998[Brewer et al, , 1999Prescott et al, 2000;Marazita et al, 2002;Zeiger et al, 2003;Blanton et al, 2004]. Different genes or regions on chromosome 2 have been implicated, including the gene for transforming growth factor alpha (TGFA) at 2p13 for CL/P [Prescott et al, 2000], the proximal part of chromosome 2q for CL/P [Riegel and Schinzel, 2002], 2q32 for CPO [Brewer et al, 1998[Brewer et al, , 1999, and 2q37 for CL/P [Zeiger et al, 2003;Blanton et al, 2004]. Riegel and Schinzel [2002] proposed that either the duplication or the disruption of a gene on the proximal part of chromosome 2q, either at 2q11.1 or at 2q13.2, may cause orofacial clefting.…”

“…Pure duplications/triplications of the proximal part of chromosome 2q have been rare. To our knowledge, only ten patients have been reported on [Wang and Hunter, 1979;Mu et al, 1984;Lanman et al, 1986;Grevengood et al, 1993;Cooke et al, 1995;Glass et al, 1998;Wang et al, 1999;Riegel and Schinzel, 2002;Wegner et al, 2004]. Clinical signs were variable and no specific 2q duplication syndrome could be defined so far [Bird and Mascarello, 2001;Riegel and Schinzel, 2002].…”

“…To our knowledge, only ten patients have been reported on [Wang and Hunter, 1979;Mu et al, 1984;Lanman et al, 1986;Grevengood et al, 1993;Cooke et al, 1995;Glass et al, 1998;Wang et al, 1999;Riegel and Schinzel, 2002;Wegner et al, 2004]. Clinical signs were variable and no specific 2q duplication syndrome could be defined so far [Bird and Mascarello, 2001;Riegel and Schinzel, 2002]. However, orofacial clefting has been considered a feature of 2q duplication/triplication [Schinzel, 2001;Riegel and Schinzel, 2002;Wegner et al, 2004] mainly because this malformation was present in four out of ten previous patients with pure proximal 2q duplication/triplication.…”

“…Clinical signs were variable and no specific 2q duplication syndrome could be defined so far [Bird and Mascarello, 2001;Riegel and Schinzel, 2002]. However, orofacial clefting has been considered a feature of 2q duplication/triplication [Schinzel, 2001;Riegel and Schinzel, 2002;Wegner et al, 2004] mainly because this malformation was present in four out of ten previous patients with pure proximal 2q duplication/triplication.…”