A de novo 10.79 Mb interstitial deletion at 2q13q14.2 involving PAX8 causing hypothyroidism and mullerian agenesis: a novel case report and literature review

作者：Ma Deqiong^*; Marion Robert; Punjabi Netra Prasad; Pereira Elaine; Samanich Joy; Agarwal Chhavi; Li Jianli; Huang Chih Kang; Ramesh K H; Cannizzaro Linda A; Naeem Rizwan

来源：Molecular Cytogenetics, 2014, 7(1): 85.

DOI：10.1186/s13039-014-0085-4

• Interstitial deletion at 2q13q14.2
• Hypothyroidism
• Mullerian agenesis

Reports of interstitial deletions involving proximal long arm of chromosome 2 are limited. Based on early chromosomal analysis studies, the phenotypic consequence of deletions at the ancestral chromosome fusion site at chromosome 2q13q14.1 remains unclear. A recurrent 1.71 Mb deletion at 2q13 has recently been proposed as a new genomic disorder, associated with an increased risk of intellectual disability and craniofacial dysmorphism. Herein, we report the case of a 12 year-old girl with unique clinical features including global developmental delay, mullerian agenesis, and hypothyroidism associated with a normal size and position of the thyroid gland, as well as negative thyroid antibodies. Microarray-based comparative genomic hybridization study revealed a de novo 10.79 Mb deletion at 2q13q14.2 (111,548,932-122,336,492), which involves more than 88 UCSC genes, 38 of which are OMIM genes, 7 of which are disease-causing and 3 of which (including GLI2, IL1B and PAX8) show a dominant inheritance pattern.. Interestingly, PAX8 (chr2:113,973,574-114,036,498), a member of the paired-box gene family, is essential for the formation of thyroxine-producing follicular cells. Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8 suggests a possible haploinsufficiency effect. Additionally, PAX8 is also expressed in the tissue primordia that form both the mullerian duct derivatives and the upper urinary tracts. A recent study has associated a novel PAX8 mutation with a severe form of hypothyroidism and abnormalities in the urogenital tract. Taken together, the unique clinical manifestation seen in this patient could be attributed to the heterozygous deletion of PAX8 gene. A prospective investigation is merited to fully evaluate the pathogenic effect of the interstitial deletion of 2q13q14.2.

• 出版日期2014-11-26