Family history is key to the interpretation of exome sequencing in the prenatal context: unexpected diagnosis of Basal Cell Nevus Syndrome.

Autor: Rinaldi B; Medical Genetics Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Cesaretti C; Medical Genetics Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Boito S; Fetal Medicine and Surgery Service, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy., Villa R; Medical Genetics Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Guerneri S; Laboratory of Medical Genetics, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Borzani I; Pediatric Radiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Rizzuti T; Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Marchetti D; Laboratorio di Genetica Medica, ASST Papa Giovanni XXIII, Bergamo, Italy., Conte G; Department of Neuroradiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy., Cinnante C; Istituto Auxologico Italiano IRCCS, Dipartimento di Radiologia e Diagnostica per Immagini, Milan, Italy., Triulzi F; Department of Neuroradiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy., Persico N; Fetal Medicine and Surgery Service, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.; Department of Clinical Science and Community Health, University of Milan, Milan, Italy., Iascone M; Laboratorio di Genetica Medica, ASST Papa Giovanni XXIII, Bergamo, Italy., Natacci F; Medical Genetics Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Jazyk: angličtina
Zdroj: Prenatal diagnosis [Prenat Diagn] 2022 Jun; Vol. 42 (7), pp. 927-933. Date of Electronic Publication: 2022 May 27.
DOI: 10.1002/pd.6171
Abstrakt: Objectives: To reach a molecular diagnosis for a family with two consecutive fetuses presenting with multiple congenital anomalies.
Methods: The two fetuses underwent prenatal ultrasound, autopsy, radiologic, and genetic investigation. Genetic analysis included karyotype and array-CGH for both fetuses and trio-based whole exome sequencing (WES) only for the second fetus.
Results: WES results, initially focusing on recessive or dominant de novo variants, were negative.However, as a result of new relevant information regarding family history, the variant c.648_651dup in the PTCH1 gene was identified as causative of the fetal phenotype.
Conclusions: This case further highlights how WES data analysis and interpretation strongly rely on family history and robust genotype-phenotype correlation. This is even more relevant in the prenatal setting, where access to fetal phenotype is limited and prenatal recognition of many morbid genes is not fully explored. We also provide a detailed description of the prenatal manifestations of Basal Cell Nevus Syndrome.
(© 2022 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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