This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bakker, B. Articles by de Vijlder, J. J. M. Search for Related Content PubMed PubMed Citation Articles by Bakker, B. Articles by de Vijlder, J. J. M.

Maternal Isodisomy for Chromosome 2p Causing Severe Congenital Hypothyroidism

Academic Medical Center, University of Amsterdam, Emma Children’s Hospital AMC, Division of Pediatric Endocrinology (B.B., H.B., T.V., J.J.M.d.V.), Department of Clinical Genetics, Institute for Clinical Genetics (M.S., R.H.), 1100 DE Amsterdam, The Netherlands; and St. Joseph Hospital, Department of Pediatrics (E.J.P.L.), 5500 MB Veldhoven, The Netherlands

Address all correspondence and requests for reprints to: Hennie Bikker, Ph.D., Academic Medical Center, University of Amsterdam, Emma Children’s Hospital AMC, Division of Pediatric Endocrinology, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail: h.bikker{at}amc.uva.nl or egbertbakker@xs4all.nl.

Severe congenital hypothyroidism (CH) due to a total iodide organification defect (TIOD) is usually due to mutations in the thyroid peroxidase (TPO) gene located at chromosome 2p25. A homozygous deletion [T2512 (codon 808)] in exon 14 was identified in a patient with classical TIOD. The transmission pattern of the TPO gene in this family was anomalous; the mother was heterozygous for the deletion; and the mutation was absent in the father. Polymorphic short tandem repeat (STR) markers confirmed paternity and demonstrated on chromosome 2 that the propositus was homozygous for most markers on chromosome 2p and that these were identical to one of the maternal 2p homologs. A normal karyotype was found in the propositus, his parents and sister. We conclude that the homozygosity in the patient is due to partial maternal isodisomy of the short arm of chromosome 2, carrying a defective TPO gene. The patient, born small for gestational age, develops and grows well and appears healthy (while being treated with thyroxine) and has a normal phenotype except for a unilateral preauricular skin tag. This shows that partial maternal isodisomy for chromosome 2p (2pter - 2p12) is compatible with a minimal influence on normal development.

This article has been cited by other articles:

				D Kotzot Complex and segmental uniparental disomy updated J. Med. Genet., September 1, 2008; 45(9): 545 - 556. [Abstract] [Full Text] [PDF]

				J. Deladoey, N. Pfarr, J.-M. Vuissoz, J. Parma, G. Vassart, S. Biesterfeld, J. Pohlenz, and G. Van Vliet Pseudodominant Inheritance of Goitrous Congenital Hypothyroidism Caused by TPO Mutations: Molecular and in Silico Studies J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 627 - 633. [Abstract] [Full Text] [PDF]

				S M Ng, S C Wong, D M Isherwood, and M Didi Biochemical severity of thyroid ectopia in congenital hypothyroidism demonstrates sexual dimorphism Eur. J. Endocrinol., January 1, 2007; 156(1): 49 - 53. [Abstract] [Full Text] [PDF]

				L. Fugazzola, N. Cerutti, D. Mannavola, G. Vannucchi, C. Fallini, L. Persani, and P. Beck-Peccoz Monoallelic Expression of Mutant Thyroid Peroxidase Allele Causing Total Iodide Organification Defect J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3264 - 3271. [Abstract] [Full Text] [PDF]

				D.-M. Niu, B. Hwang, Y.-K. Chu, C.-J. Liao, P.-L. Wang, and C.-Y. Lin High Prevalence of a Novel Mutation (2268 insT) of the Thyroid Peroxidase Gene in Taiwanese Patients with Total Iodide Organification Defect, and Evidence for a Founder Effect J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4208 - 4212. [Abstract] [Full Text] [PDF]