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A new sporadic case of early-onset Loeys-Dietz syndrome due to the recurrent mutation p.R528C in the TGFBR2 gene substantiates interindividual clinical variability

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Jamsheer A., Henggeler C., Wierzba J., Loeys B., De_ P. A., Stheneur C., Badziag N., Matuszewska K., Matyas G., Latos-Bielenska A.

Journal of Applied Genetics

2009

vol. 50

issue 4

405-410

We report on a 2-year-old Polish girl with typical manifestations of Loeys-Dietz syndrome (LDS), a rare genetic condition belonging to the group of Marfan-related disorders. The characteristic LDS symptoms observed in the girl included craniofacial dysmorphism (craniosynostosis, cleft palate, hypertelorism), arachnodactyly, camptodactyly, scoliosis, joint laxity, talipes equinovarus, translucent and hyperelastic skin, and umbilical hernia. Mild dilatation of the ascending aorta and tortuous course of the left internal carotid artery were recognized during her second year of life. Molecular genetic testing revealed a heterozygous missense mutation (c.1582C>T, p.R528C) in the transforming growth factor beta receptor II gene (TGFBR2). This mutation has been previously associated with LDS in 5 unrelated cases, and was never reported in patients with other Marfan-related disorders. Comparison of the phenotypes of our patient and these 5 individuals with c.1582C>T showed that only the hallmark triad of the syndrome ? consisting of hypertelorism, aortic root dilatation/aneurysm, and cleft palate or bifid uvula ? was present in all 6 cases. Interestingly, none of the 5 individuals who underwent psychological evaluation showed developmental delay. The pattern of all other LDS features showed interindividual variability. Our data support the recently reported observation that symptoms of LDS can develop at a very young age, making early diagnosis and management essential for these patients. This is the first report on a Polish infant with typical LDS symptoms caused by a TGFBR2 mutation.

Subtle familial translocation t(11;22)(q24.2;q13.33) resulting in Jacobsen syndrome and distal trisomy 22q13.3: further details of genotype?phenotype maps

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Jamsheer A., Smyk M., Wierzba J., Kolowska J., Wozniak A., Skolozdrzy J., Fischer M., Latos-Bielenska A.

Journal of Applied Genetics

2008

vol. 49

issue 4

397-405

We report on 3 kindred patients with terminal 11q monosomy and distal 22q trisomy involving the SHANK3 gene, resulting from a subtle familial translocation t(11;22)(q24.2;q13.33). The patients presented with the characteristic symptoms of Jacobsen syndrome (JBS), including: mental retardation, short stature, and craniofacial dysmorphism in all 3 cases; cardiac defects in 2 cases; and thrombocytopenia, brain abnormality, eye coloboma, recurrent infections, cryptorchidism and toe anomalies in single cases. The oldest patient also had Hashimoto disease and diabetes mellitus type 2. So far, these 2 conditions have not been reported in adult patients with JBS. Features typical for distal 22q trisomy in our patients include muscular hypotonia and prenatal failure to thrive, seen in 2 and 1 cases, respectively. We also present a family member with 11q24.2-qter trisomy and 22q13.33-qter monosomy, whose clinical phenotype is partially overlapping with several dysmorphic features of JBS. In addition, multiple pregnancy losses and infantile deaths occurred in this family, suggesting that these chromosomal imbalances may produce a lethal phenotype. FISH with a panel of BAC probes determined the accurate sizes of the deletion 11q (9.9 Mb) and trisomy 22q (0.8 Mb). To date, only 5 cases of submicroscopic 22q13.3-qter trisomy have been reported. A detailed clinical description of our patients, along with a precise cytogenetic designation of chromosomal breakpoints, allow further refinement of genotype-phenotype correlation for distal imbalances in 11q and 22q.

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2 Journal of Applied Genetics

1 2009

1 2008

2 Jamsheer A.

2 Latos-Bielenska A.

2 Wierzba J.

1 Badziag N.

1 De_ P. A.

1 Fischer M.

1 Henggeler C.

1 Kolowska J.

1 Loeys B.

1 Matuszewska K.

1 Matyas G.

1 Skolozdrzy J.

1 Smyk M.

1 Stheneur C.

1 Wozniak A.

Search results

A new sporadic case of early-onset Loeys-Dietz syndrome due to the recurrent mutation p.R528C in the TGFBR2 gene substantiates interindividual clinical variability

Subtle familial translocation t(11;22)(q24.2;q13.33) resulting in Jacobsen syndrome and distal trisomy 22q13.3: further details of genotype?phenotype maps