title: 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.
abstract: 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.
authors.affiliation: Molecular Pathology and Cytogenetics Lab, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, 1635 Poplar Street, Bronx, NY 10461 USA.
authors.forename: Deqiong
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Pediatrics, Children's Hospital at Montefiore, Bronx, NY USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Marion
authors.affiliation: Department of Pediatrics, Children's Hospital at Montefiore, Bronx, NY USA.
authors.forename: Netra Prasad
authors.initials: NP
authors.lastname: Punjabi
authors.affiliation: Department of Pediatrics, Children's Hospital at Montefiore, Bronx, NY USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Pereira
authors.affiliation: Department of Pediatrics, Children's Hospital at Montefiore, Bronx, NY USA.
authors.forename: Joy
authors.initials: J
authors.lastname: Samanich
authors.affiliation: Department of Pediatrics, Children's Hospital at Montefiore, Bronx, NY USA.
authors.forename: Chhavi
authors.initials: C
authors.lastname: Agarwal
authors.affiliation: Molecular Pathology and Cytogenetics Lab, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, 1635 Poplar Street, Bronx, NY 10461 USA.
authors.forename: Jianli
authors.initials: J
authors.lastname: Li
authors.affiliation: Molecular Pathology and Cytogenetics Lab, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, 1635 Poplar Street, Bronx, NY 10461 USA.
authors.forename: Chih-Kang
authors.initials: CK
authors.lastname: Huang
authors.affiliation: Molecular Pathology and Cytogenetics Lab, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, 1635 Poplar Street, Bronx, NY 10461 USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Ramesh
authors.affiliation: Molecular Pathology and Cytogenetics Lab, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, 1635 Poplar Street, Bronx, NY 10461 USA.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Cannizzaro
authors.affiliation: Molecular Pathology and Cytogenetics Lab, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, 1635 Poplar Street, Bronx, NY 10461 USA.
authors.forename: Rizwan
authors.initials: R
authors.lastname: Naeem
keywords: Hypothyroidism; Interstitial deletion at 2q13q14.2; Mullerian agenesis