Maternal Isodisomy for Chromosome 2p Causing Severe Congenital Hypothyroidism

Bakker, Bert; Bikker, Hennie; Hennekam, Raoul C. M.; Lommen, E. J. P.; Schipper, Mei; Vulsma, Thomas; Vijlder, J J de

doi:10.1210/jcem.86.3.7313

Cited by 35 publications

(14 citation statements)

References 19 publications

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“…He has a normal phenotype except for a unilateral preauricular skin tag. This shows that partial maternal isodisomy (2pter -2p12) is compatible with no or a minimal influence on normal development (62).…”

Section: Iodide Organification Defectsmentioning

confidence: 72%

Primary congenital hypothyroidism: defects in iodine pathways

Vijlder

2003

European Journal of Endocrinology

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The thyroid gland is the only source of thyroid hormone production. Thyroid hormone is essential for growth and development, and is of special importance for the development of the central nervous system. It was for that reason that neonatal screening on congenital hypothyroidism was introduced and is now performed in many countries. Defects in thyroid hormone production are caused by several disorders in hormone synthesis and in the development of the thyroid gland (primary hypothyroidism) or of the pituitary gland and hypothalamus (central hypothyroidism). This paper describes defects in the synthesis of thyroid hormone caused by disorders in the synthesis or iodination of thyroglobulin, leakage of iodinated proteins by a stimulated thyroid gland and the presence of abnormal iodoproteins, mainly iodinated albumin, in the thyroid gland and blood circulation. Circulating thyroglobulin and abnormal iodoproteins, as well as the breakdown products of these iodoproteins excreted in urine, are used for etiological diagnosis and classification. Moreover, our finding of an enzyme that catalyses the dehalogenation of iodotyrosines, which is important for iodine recycling and required for economical use of iodine, is also referred to.

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Section: Iodide Organification Defectsmentioning

confidence: 72%

Primary congenital hypothyroidism: defects in iodine pathways

Vijlder

2003

European Journal of Endocrinology

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“…TPO is a thyroid peroxidase enzyme playing a key role in thyroid hormone biosynthesis. However, the total iodide organification defect, cause of severe congenital hypothyroidism, is a recessively inherited disorder by mutations in the TPO gene [Bakker et al, 2001]. Thus, haploinsufficiency of the TPO gene may not directly be involved in the severe phenotype.…”

Section: Discussionmentioning

confidence: 99%

Recurrent inverted duplication of 2p with terminal deletion in a patient with the classical phenotype of trisomy 2p23‐pter

Gruchy

Jacquemont

Lyonnet

et al. 2007

American J of Med Genetics Pt A

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Inverted duplications with terminal deletions have been reported in an increasing number of chromosomes and are probably more frequent than suspected until recently. We describe the cytogenetic and molecular characterization of an inverted duplication of chromosome 2p in an 8-year-old girl. Firstly interpreted as partial duplication 2p, the rearrangement was in fact an inverted duplication associated with a terminal deletion of the short arm of the rearranged chromosome 2, the latter not being detectable by cytogenetic analysis. The complete karyotype was: 46,XX,add(2)(p23)dn.ish inv dup del(2)(:p23.2-->p25.3::p25.3-->qter) (wcp2+,N-MYC++,2pter-)dn. We precisely define the extension of both the duplication and the deletion using bacterial artificial chromosomes clones spanning the regions. The size of the inverted duplicated segment was estimated to be 28 Mb, spanning from 2p23.2 to 2p25.3, and an approximately 1.6 Mb segment at 2pter-p25.3 was deleted in the abnormal chromosome. The physical findings noted in our patient include prominent forehead, hypertelorism, flat nasal bridge, and low-set and large ears. In addition, she had congenital heart defect and scoliosis. Her psychomotor development was severely delayed from the beginning. All these clinical features are the same as observed for the typical trisomy 2p23-pter syndrome. The phenotypic effects of the terminal deletion of 2p in addition to the trisomy are discussed. This is the third patient presenting with a severe clinical phenotype and a de novo inv dup del (2p).

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“…In recent years, much progress has been made in the clarification and identification of thyroid defects at a molecular level. Recent advances in molecular genetics have also led to characterisation of numerous genes essential for the normal development of the thyroid gland (16)(17)(18)(19). Thyroid disorders may be a polygenic disease or have a multifactorial basis.…”

Section: Discussionmentioning

confidence: 99%

“…Another cause of CH is a mutation of one of the genes encoding for the thyroid transcription factors: TTF-1, TTF-2 or paired box gene 8 (PAX-8). These have been described as candidate genes for thyroid ectopy, and they play a key role in controlling thyroid gland morphogenesis, differentiation and normal development and migration of the thyroid gland in the foetus (16)(17)(18)(19). Recent advancements in genome sequencing and molecular technology have also provided further insights into the study of genes that are differentially expressed in each sex in a variety of tissues (20).…”

Section: Discussionmentioning

confidence: 99%

Biochemical severity of thyroid ectopia in congenital hypothyroidism demonstrates sexual dimorphism

Wong²,

Isherwood³

et al. 2007

eur j endocrinol

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Background: A recent study suggested that sexual dimorphism affects initial thyroid function in congenital hypothyroidism (CH) but differs according to aetiology of CH. Aims: To determine if sexual dimorphism was associated with biochemical severity of CH and its aetiology in our large British population. Methods: We examined retrospectively the initial thyroid function tests of 140 infants diagnosed with CH from screening. All infants underwent Tc-pertechnetate radionuclide scans at diagnosis to establish the aetiology of CH prior to commencement of treatment. Patients were classified into athyreosis, ectopia and presumed dyshormonogenesis on the basis of thyroid scans. A comparison of males and females were made within the three aetiological groups for gestational age, birth weight, initial dose of levothyroxine (LT4), screening TSH, confirmatory plasma thyroxine (T4), confirmatory plasma TSH and age of TSH suppression. Results: There was no significant difference between sexes for gestation, birth weight and initial treatment dose in all aetiological subgroups. In thyroid ectopia, screening TSH and confirmatory plasma TSH were significantly higher in females compared with males (P!0.01), while confirmatory plasma T4 were significantly lower in females (P!0.05). No difference was detected between males and females in athyreosis and dyshormonogenesis subgroups for screening TSH, confirmatory plasma TSH and total T4. Conclusion: Sexual dimorphism influenced the biochemical severity of thyroid ectopia in congenital hypothyroidism in our British population. However, this effect was not apparent in patients with athyreosis or dyshormonogenesis. Further advances in the molecular genetics of CH are essential to evaluate this phenomenon further.

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Maternal Isodisomy for Chromosome 2p Causing Severe Congenital Hypothyroidism

Cited by 35 publications

References 19 publications

Primary congenital hypothyroidism: defects in iodine pathways

Primary congenital hypothyroidism: defects in iodine pathways

Recurrent inverted duplication of 2p with terminal deletion in a patient with the classical phenotype of trisomy 2p23‐pter

Biochemical severity of thyroid ectopia in congenital hypothyroidism demonstrates sexual dimorphism

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