Author:
Nayak Shalini S.,Schneeberger Pauline E.,Patil Siddaramappa J.,Arun Karegowda M.,Suresh Pujar V.,Kiran Viralam S.,Siddaiah Sateesh,Maiya Shreesha,Venkatachalagupta Shrikanth K.,Kausthubham Neethukrishna,Kortüm Fanny,Rau Isabella,Wey-Fabrizius Alexandra,Van Den Heuvel Lotte,Meester Josephina,Van Laer Lut,Shukla Anju,Loeys Bart,Girisha Katta M.,Kutsche Kerstin
Abstract
AbstractMarfan syndrome and related disorders are a group of heritable connective tissue disorders and share many clinical features that involve cardiovascular, skeletal, craniofacial, ocular, and cutaneous abnormalities. The majority of affected individuals have aortopathies associated with early mortality and morbidity. Implementation of targeted gene panel next-generation sequencing in these individuals is a powerful tool to obtain a genetic diagnosis. Here, we report on clinical and genetic spectrum of 53 families from India with a total of 83 patients who had a clinical diagnosis suggestive of Marfan syndrome or related disorders. We obtained a molecular diagnosis in 45/53 (85%) index patients, in which 36/53 (68%) had rare variants in FBN1 (Marfan syndrome; 63 patients in total), seven (13.3%) in TGFBR1/TGFBR2 (Loeys–Dietz syndrome; nine patients in total) and two patients (3.7%) in SKI (Shprintzen–Goldberg syndrome). 21 of 41 rare variants (51.2%) were novel. We did not detect a disease-associated variant in 8 (15%) index patients, and none of them met the Ghent Marfan diagnostic criteria. We found the homozygous FBN1 variant p.(Arg954His) in a boy with typical features of Marfan syndrome. Our study is the first reporting on the spectrum of variants in FBN1, TGFBR1, TGFBR2, and SKI in Indian individuals.
Funder
Fund for Scientific Research, Flanders
Universiteit Antwerpen
The Dutch Heart Foundation
Marfan Foundation
European Research Council
Indian Council of Medical Research
Bundesministerium für Bildung und Forschung
Projekt DEAL
Publisher
Springer Science and Business Media LLC
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