A 300-kb microduplication of 7q36.3 in a patient with triphalangeal thumb-polysyndactyly syndrome combined with congenit
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Open Access
CASE REPORT
A 300‑kb microduplication of 7q36.3 in a patient with triphalangeal thumb‑polysyndactyly syndrome combined with congenital heart disease and optic disc coloboma: a case report Anna Zlotina1* , Olesia Melnik1, Yulia Fomicheva1, Rostislav Skitchenko2, Alexey Sergushichev2, Elena Shagimardanova3, Oleg Gusev3,4, Guzel Gazizova3, Tatiana Loevets1, Tatiana Vershinina1, Ivan Kozyrev1, Mikhail Gordeev1, Elena Vasichkina1, Tatiana Pervunina1 and Anna Kostareva1,5*
Abstract Background: Triphalangeal thumb-polysyndactyly syndrome (TPT-PS) is a rare well-defined autosomal dominant disorder characterized by long thumbs with three phalanges combined with pre- and postaxial polydactyly/syndactyly of limbs.By now, the syndrome has been reported in several large families from different ethnic backgrounds, with a high degree of inter- and intrafamilial variability. The genome locus responsible for TPT-PS has been mapped to the 7q36.3 region harboring a long-range sonic hedgehog (SHH) regulatory sequence (ZRS). Both single-nucleotide variants and complete duplications of ZRS were shown to cause TPT-PS and similar limb phenotypes. TPT-PS usually forms as isolated limb pathology not associated with additional malformations, in particular, with cardiovascular abnormalities. Case presentation: Here we report on a rare Russian neonatal case of TPT-PS combined with severe congenital heart disease, namely double outlet right ventricle, and microphthalmia with optic disc coloboma. Pedigree analysis revealed TPT-PS of various expressivity in 10 family members throughout five generations, while the cardiac defect and the eye pathology were detected only in the proband. To extend the knowledge on genotype–phenotype spectrum of TPT-PS, the careful clinical and genomic analysis of the family was performed. High-resolution array-based comparative genomic hybridization (array-CGH) revealed a ~ 300 kb microduplication of 7q36.3 locus (arr[GRCh37] 7q36.3(156385810_156684811) × 3) that co-segregated with TPT-PS in the proband and her mother. The duplication encompassed three genes including LMBR1, the intron 5 of which is known to harbor ZRS. Based on whole-exome sequencing data, no additional pathogenic mutations or variants of uncertain clinical significance were found in morbid cardiac genes or genes associated with a microphthalmia/anophthalmia/coloboma spectrum of ocular malformations.
*Correspondence: anna‑[email protected]; [email protected] 1 Almazov National Medical Research Centre, 2, Akkuratova Street, Saint Petersburg, Russia 197341 Full list of author information is available at the end of the article © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third part
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