Schilbach-Rott syndrome associated with 9q22.32q22.33 duplication, involving the PTCH1 gene
| Autor: | Daniela Rogaia, Giuseppe Merla, Susanna Esposito, Danilo Moretti-Ferreira, Amedea Mencarelli, Gabriella Maria Squeo, Paolo Prontera, Sandro Elisei, Gabriela Stangoni, Valentina Imperatore, Ester Sallicandro |
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| Přispěvatelé: | Prontera, P, Rogaia, D, Sallicandro, E, Mencarelli, A, Imperatore, V, Squeo, Gm, Merla, G, Elisei, S, Moretti-Ferreira, D, Esposito, S, Stangoni, G |
| Rok vydání: | 2019 |
| Předmět: |
Proband
Male congenital hereditary and neonatal diseases and abnormalities Biology Article Craniofacial Abnormalities 03 medical and health sciences Fathers Holoprosencephaly Hypotelorism Gene Duplication Intellectual Disability Gene duplication parasitic diseases Chromosome Duplication Genetics medicine Humans Child Gene Genetics (clinical) 0303 health sciences Comparative Genomic Hybridization Hypospadias 030305 genetics & heredity PTCH1 Gene medicine.disease Phenotype Cleft Palate Patched-1 Receptor PTCH1 Female Chromosomes Human Pair 9 |
| Zdroj: | Eur J Hum Genet |
| Popis: | Schilbach-Rott syndrome (SRS, OMIM% 164220) is a disorder of unknown aetiology that is characterised by hypotelorism, epichantal folds, cleft palate, dysmorphic face, hypospadia in males and mild mental retardation in some patients. To date, 5 families and 17 patients have exhibited this phenotype, and recurrence in two of these families suggests an autosomal dominant inheritance. SRS overlaps with a mild form of holoprosencephaly (HPE), but array-CGH analysis and sequencing of some HPE-related genes (SEPT9, SHH and TWIST) did not reveal any variants in at least one family. Herein, we investigated by array-CGH analysis a 11-year-old female patient and her father, both exhibiting the typical SRS phenotype, disclosing in the daughter-father couple the same microduplication of chromosome 9q22.32q22.33 [arr[hg19]9q22.32 (98,049,611_98,049,636) x3,9q22.33 (99,301,483_99,301,508)x3], involving eight genes, including PTCH1. The duplication segregated with the disease, since it was not found in the healthy paternal grandparents of the proband. The gain-of-function variants of the PTCH1 gene are responsible for a mild form of HPE. This is the first genetic variant found in SRS. This finding reinforces the hypothesis that SRS belongs to the HPE clinical spectrum and suggests to perform array-CGH in patients with SRS phenotype and, if negative, to consider a potential benefit from sequencing of HPE-related genes. |
| Databáze: | OpenAIRE |
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