American Journal of Medical Genetics Part AVolume 140A, Issue 10 p. 1111-1113 Research Letter A balanced reciprocal translocation in a case of hypomelanosis of Ito with confirmation of mosaicism using buccal cell interphase FISH† W.T. Keng, W.T. Keng Clinical Genetics Department, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorL. Harewood, L. Harewood MRC Human Genetic Unit, MRC, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorE. Grace, E. Grace Lothian Regional Cytogenetic Laboratory, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorC. Paxton, C. Paxton Lothian Regional Cytogenetic Laboratory, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorW.W.K. Lam, W.W.K. Lam Clinical Genetics Department, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorD.R. FitzPatrick, Corresponding Author D.R. FitzPatrick [email protected] Clinical Genetics Department, Western General Hospital, Edinburgh, United Kingdom MRC Human Genetic Unit, MRC, Western General Hospital, Edinburgh, United KingdomMRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2X, UK.Search for more papers by this author W.T. Keng, W.T. Keng Clinical Genetics Department, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorL. Harewood, L. Harewood MRC Human Genetic Unit, MRC, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorE. Grace, E. Grace Lothian Regional Cytogenetic Laboratory, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorC. Paxton, C. Paxton Lothian Regional Cytogenetic Laboratory, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorW.W.K. Lam, W.W.K. Lam Clinical Genetics Department, Western General Hospital, Edinburgh, United KingdomSearch for more papers by this authorD.R. FitzPatrick, Corresponding Author D.R. FitzPatrick [email protected] Clinical Genetics Department, Western General Hospital, Edinburgh, United Kingdom MRC Human Genetic Unit, MRC, Western General Hospital, Edinburgh, United KingdomMRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2X, UK.Search for more papers by this author First published: 04 April 2006 https://doi.org/10.1002/ajmg.a.31190Citations: 3 † How to cite this article: Keng WT, Harewood L, Grace E, Paxton C, Lam WWK, FitzPatrick DR. 2006. A balanced reciprocal translocation in a case of hypomelanosis of Ito with confirmation of mosaicism using buccal cell interphase FISH. Am J Med Genet Part A 140A:1111–1113. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL REFERENCES Aughton DJ, AlSaadi AA, Canady AI, Lucas BM. 1993. Balanced reciprocal translocation mosaicism associated with an abnormal phenotype. Am J Med Genet 45: 721– 724. Cole TR, Hughes HE. 1994. Sotos syndrome: A study of the diagnostic criteria and natural history. J Med Genet 31: 20– 32. Duba HC, Doll A, Neyer M, Erdel M, Mann C, Hammerer I, Utermann G, Grzeschik KH. 2002. 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Stoll C, Alembik Y, Grosshans E, de Saint Martin A. 2002. An unusual human mosaic for skin pigmentation. Genet Couns 13: 281– 287. Vargas MT, Fernandez-Novoa MC. 2001. Balanced reciprocal translocation mosaicism: Clinical implications. Two new cases. Genet Couns 12: 269– 271. Citing Literature Volume140A, Issue1015 May 2006Pages 1111-1113 ReferencesRelatedInformation

We report heterozygous, loss-of-function SOX2 mutations in three unrelated individuals with Anophthalmia-Esophageal-Genital (AEG) syndrome. One previously reported case [Rogers, R.C. (1988) Unknown cases. Proceedings of the Greenwood Genetic Center. 7, 57.] has a 2.7 Mb deletion encompassing SOX2 and associated with a cryptic translocation t(3;7)(q28;p21.3). The deletion and translocation breakpoints on chromosome 3q are >8.6 Mb apart and both chromosome rearrangements have occurred de novo. Another published case [Petrackova et al. (2004) Association of oesophageal atresia, anophthalmia and renal duplex. Eur. J. Pediatr., 163, 333-334.] has a de novo nonsense mutation, Q55X. A previously unreported case with severe bilateral microphthalmia and oesophageal atresia has a de novo missense mutation, R74P, that alters a highly evolutionarily conserved residue within the high mobility group domain, which is critical for DNA-binding of SOX2. In a yeast one-hybrid assay, this mutation abolishes Sox2-induced activation of the chick delta-crystallin DC5 enhancer. Four other reported AEG syndrome cases were extensively screened and do not have detectable SOX2 mutations. Two of these cases have unilateral eye malformations. SOX2 mutations are known to cause severe bilateral eye malformations but this is the first report implicating loss of function mutations in this transcription factor in oesophageal malformations. SOX2 is expressed in the developing foregut in mouse and zebrafish embryos and an apparently normal pattern of expression is maintained in Shh-/- mouse embryos, suggesting either that Sox2 acts upstream of Shh or functions in a different pathway. Three-dimensional reconstructions of the major morphological events in the developing foregut and eye from Carnegie Stages 12 and 13 human embryos are presented and compared with the data from model organisms. SOX2, with NMYC and CHD7, is now the third transcriptional regulator known to be critical for normal oesophageal development in humans.

The mitochondrial transfer ribonucleic acid for leucine is encoded by nucleotides 3230-3304. A-to-G transition at nucleotide 3243 can cause maternally transmitted diabetes mellitus-deafness syndrome, and MELAS syndrome. MELAS syndrome is a rare disorder of mitochondrial energy production, and is an acronym for myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. Cortical malformations are heterogeneous and result from abnormal cell proliferation/apoptosis, migration, and/or differentiation of neuroepithelial cells. They are an important and relatively common cause of intractable epilepsy and neurodevelopmental disorders. The association between these A3243G mutations and cortical malformation has never before been reported. Here a 14-year-old female with A3243G mutation and polymicrogyria is described and possible aetiologies of this association are discussed.

We report a seven generation family in which a 2;11 chromosome translocation is segregating. Both unbalanced segregants have been found in the family, and cytogenetic analysis demonstrates that this results in effective monosomy or trisomy for chromosome band 2q37.3. Those family members who are monosomic exhibit a variable phenotype with a number of features associated with an Albright's Hereditary Osteodystrophy-like phenotype (AHO-like) whilst those who are trisomic have a phenotypic spectrum ranging from mild facial anomalies and growth retardation to apparent normality. The latter group of patients represent the first reported patients with pure trisomy for chromosome band 2q37.3.

We report three children with food aversion and characteristic facial dysmorphism, long digits and genitourinary abnormality. Interrogation of the London Dysmorphology Database suggests that this is a previously unreported syndrome.