ESPN 50th Annual Meeting

ESPN 2017


 
A rare inherited disease in two twin siblings
HANAN .M. FATHY 1 DANIELA .A. BRAUN 2 FRIEDHELM HILDEBRANDT 2

1- Pediatric nephrology unit, University of Alexandria, Egypt
2- Division of Nephrology, Harvard Medical School, Boston Children’s Hospital, Boston, USA
 
Introduction:

 Objective: To identify the molecular disease cause in two twin siblings with nephrotic syndrome and dysmorphic features, we performed mutational analysis. 

Material and methods:

 Through a collaborative work, the two cases were studied with regards to their phenotype in the pediatric nephrology unit at the faculty of medicine, university of Alexandria, and mutation analysis was performed in the Hildebrandt lab at BostonsChildren Hospital, Harvard MedicalSchool. To identify the causative mutation in these two siblings born of consanguineous union, we combined whole exome sequencing with homozygosity mapping. 

Results:

 The two twin siblings, the outcome of consanguineous marriage,were a boy and a girl, who presented with short stature, dysmorphic facial features, skeletal anomalies,and hypothyroidism. Furthermore, the boy had congenital heart disease, and he presented with nephrotic syndrome, that rapidly progressed to end stage kidney disease, while the girl only showed nephrotic range proteinuria without renal impairment. Whole exome sequencing revealed a homozygous mutation in the gene COG1 that segregated with the affected status in this family. The mutated allele is likely deleterious as it has never been reported in healthy control databases (i.e. ExAC or gnomAD) and affects a well-conserved splice site. Mutations in the gene COG1 have been previously described in two unrelated families as monogenic causes of cerebrocostomandibular-like syndrome (MIM# 611209). However, renal involvement has not been described yet in patients with COG1 mutations.  

Conclusions:

 By whole exome and homozygosity mapping, we identified a rare genetic syndrome as the molecular disease cause in these siblings. We expand the phenotypic spectrum of COG1 mutations by describing renal involvement for the first time in this monogenic disease.