Open AccessDual Diagnosis of Ellis-van Creveld Syndrome and Hearing Loss in a Consanguineous Family
Author(s) -
Barbara Vona,
Reza Maroofian,
Geetu Mendiratta,
Matthew McKnight Croken,
Siwu Peng,
Xiaoqian Ye,
Jamileh Rezazadeh,
Paulina Bahena,
Caroline Lekszas,
Thomas Haaf,
Lisa Edelmann,
Lisong Shi
Publication year - 2017
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000480458
Subject(s) - proband , phenotype , genetic heterogeneity , hearing loss , genetics , medicine , genetic testing , genetic disorder , genetic counseling , medical genetics , biology , gene , mutation , audiology
Multilocus analysis of rare or genetically heterogeneous diseases is a distinct advantage of next-generation sequencing (NGS) over conventional single-gene investigations. Recent studies have begun to uncover an under-recognized prevalence of dual molecular diagnoses in patients with a "blended" phenotype that is the result of 2 clinical diagnoses involving 2 separate genetic loci. This blended phenotype could be mistakenly interpreted as a novel clinical extension of a single-gene disorder. In this study, we ascertained a proband from a large consanguineous Iranian family who manifests postlingual, progressive, moderate hearing loss in addition to suspected Ellis-van Creveld syndrome phenotype. NGS with a customized skeletal dysplasia panel containing over 370 genes and subsequent bioinformatics analysis disclosed 2 homozygous mutations in EVC2 (c.2653C>T; p.Arg885*) and COL11A2 (c.966dup; p.Thr323His fs *19), respectively. This study highlights a dual molecular diagnosis in a patient with a blending of 2 distinct phenotypes and illustrates the advantage and importance of this staple technology to facilitate rapid and comprehensive genetic dissection of a heterogeneous phenotype. The differentiation between phenotypic expansion of a genetic disorder and a blended phenotype that is due to more than one distinct genetic aberration is essential in order to reduce the diagnostic odyssey endured by patients.