Increased Probability of Co-Occurrence of Two Rare Diseases in Consanguineous Families and Resolution of a Complex Phenotype by Next Generation Sequencing.

ABSTRACT: Massively parallel sequencing of whole genomes and exomes has facilitated a direct assessment of causative genetic variation, now enabling the identification of genetic factors involved in rare diseases (RD) with Mendelian inheritance patterns on an almost routine basis. Here, we describe the illustrative case of a single consanguineous family where this strategy suffered from the difficulty to distinguish between two etiologically distinct disorders, namely the co-occurrence of hereditary hypophosphatemic rickets (HRR) and congenital myopathies (CM), by their phenotypic manifestation alone. We used parametric linkage analysis, homozygosity mapping and whole exome-sequencing to identify mutations underlying HRR and CM. We also present an approximate approach for assessing the probability o

SUBMITTER: Lal D 

PROVIDER: S-EPMC4720433 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature