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Xq27.1 Duplication Encompassing <b><i>SOX3</i></b>: Variable Phenotype and Smallest Duplication Associated with Hypopituitarism to Date – A Large Case Series of Unrelated Patients and a Literature Review

2019; Karger Publishers; Volume: 92; Issue: 6 Linguagem: Inglês

10.1159/000503784

1663-2826

Ved Bhushan Arya, Garima Chawla, Aparna K.R. Nambisan, Nadia Muhi-Iddin, Ekaterini Vamvakiti, Michal Ajzensztejn, Tony Hulse, Clare Ferreira Pinto, Nayana Lahiri, Susan Bint, Charles Buchanan, Ritika R. Kapoor,

Chromatin Remodeling and Cancer

<b><i>Background:</i></b> Xq27.1 duplication encompassing <i>SOX3</i> has been implicated in the aetiology of X-linked hypopituitarism associated with intellectual disability and neural tube defects. We describe the largest case series to date of 5 unrelated patients with <i>SOX3</i> duplication with a variable clinical phenotype, including the smallest reported <i>SOX3</i> duplication. <b><i>Case Reports:</i></b> Five male patients who presented with congenital hypopituitarism (CH) were identified to have Xq27.1 duplication encompassing <i>SOX3</i>. The size of the duplication ranged from 323.8 kb to 11 Mb. The duplication was maternally inherited or de novo in 2 patients each (and of unknown inheritance in 1 patient). The age at presentation was variable. Three patients had multiple pituitary hormone deficiencies, whereas 2 patients had isolated growth hormone deficiency. All patients had micropenis and/or small undescended testes. Structural pituitary and/or other midline cranial abnormalities (callosal hypogenesis/absence of the septum pellucidum) were present in all patients. Two patients had a neural tube defect in addition to CH. <b><i>Conclusions:</i></b> This is the largest series reported to date of unrelated patients with CH in association with Xq27.1 duplication encompassing <i>SOX3</i>. The clinical phenotype is variable, which may be due to genetic redundancy or other unknown aetiological factors. We have expanded the phenotypic spectrum through description of the smallest Xq27.1 duplication (323.8 kb) with CH reported to date, as well as a second family with CH and a neural tube defect.