Open AccessTwo Novel Pathogenic MID1 Variants and Genotype-Phenotype Correlation Reanalysis in X-Linked Opitz G/BBB Syndrome
Author(s) -
Nuno Maia,
Maria João Nabais Sá,
Natáliya Tkachenko,
Gabriela Soares,
Isabel Marques,
Bárbara Rodrigues,
A Fortuna,
Rosário Santos,
Arjan P.M. de Brouwer,
Paula Jorge
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 - 10.1159/000479177
Subject(s) - hypertelorism , phenotype , genetics , genotype , intellectual disability , genotype phenotype distinction , mutation , loss function , hypospadias , medicine , hearing loss , biology , gene , audiology
X-linked Opitz G/BBB syndrome (XLOS) is a multisystemic congenital condition, caused by mutations in the midline-1 gene ( MID1 ), characterized by a large inter- and intrafamilial phenotypic variability and often associated with intellectual disability (ID). We report clinical, genetic, and molecular findings in 4 patients with typical XLOS dysmorphic features belonging to 2 unrelated families. Two novel pathogenic loss-of-function MID1 variants, a maternally inherited c.1656del and a de novo c.1215_1228dup, were identified. Subsequently, we performed a genotype-phenotype analysis using data from 91 male XLOS patients. To test the mutation impact on the phenotype; the type of mutation, the MID1-impaired domain and function were compared with the presence of each of the major clinical features (hypertelorism, clefts of the lip and/or palate, laryngo-tracheo-esophageal abnormalities, hypospadias and ID) and minor clinical features (brain, heart, and anal defects). No statistically significant correlation was found with these features. Further investigations, as well as exhaustive and unequivocal phenotyping, may be required to improve our knowledge of the biological mechanisms underlying this syndrome and to provide more adequate disease management.