15q26 deletion in a patient with congenital heart defect, growth restriction and intellectual disability: case report and literature review.

BACKGROUND: 15q26 deletion is a relatively rare chromosomal disorder, and it is described only in few cases. Patients with this aberration show many signs and symptoms, particularly pre- and postnatal growth restriction, developmental delay, microcephaly, intellectual disability and various congenital malformations. CASE PRESENTATION: We report on a girl, 4 years old, of consanguineous parents, with a 15q26 deletion. Clinical manifestations included failure to thrive, developmental delay, microcephaly, dysmorphic facies with broad forehead, hypertelorism, narrowed eyelid slits and protruding columella. The patient also showed skeletal abnormalities, especially clinodactyly of the 5th finger, varus equine right foot and left club foot. Additionally, she had teething delay and divergent strabismus. Heart ultrasound displayed two atrial septal defects with left-to-right shunt, enlarging the right cavities. Routine cytogenetic analysis revealed a shortened 15q chromosome. Subsequent array analysis disclosed a terminal 9.15 Mb deletion at subband 15q26.1-q26.3. Four candidate genes associated with 15q26 deletion phenotype were within the deleted region, i.e. IGF1R, NR2F2, CHD2 and MEF2A. CONCLUSION: We report on an additional case of 15q26 monosomy, characterized by array-CGH. Molecular cytogenetic analysis allowed us to identify the exact size of the deletion, and four candidate genes for genotype-phenotype correlation. 15q26 monosomy should be considered when growth retardation is associated with hearing anomalies and congenital heart defect, especially atrioventricular septal defects (AVSDs) and/or aortic arch anomaly (AAA).

Novel mutation in the TGFBI gene in a Moroccan family with atypical corneal dystrophy: a case report.

BACKGROUND: Corneal dystrophies (CDs) are a heterogeneous group of bilateral, genetically determined, noninflammatory bilateral corneal diseases that are usually limited to the cornea. CD is characterized by a large variability in the age of onset, evolution and visual impact and the accumulation of insoluble deposits at different depths in the cornea. Clinical symptoms revealed bilateral multiple superficial, epithelial, and stromal anterior granular opacities in different stages of severity among three patients of this family. A total of 99 genes are involved in CDs. The aim of this study was to identify pathogenic variants causing atypical corneal dystrophy in a large Moroccan family and to describe the clinical phenotype with severely different stages of evolution. CASE PRESENTATION: In this study, we report a large Moroccan family with CD. Whole-exome sequencing (WES) was performed in the three affected members who shared a phenotype of corneal dystrophy in different stages of severity. Variant validation and familial segregation were performed by Sanger sequencing in affected sisters and mothers and in two unaffected brothers. Whole-exome sequencing showed a novel heterozygous mutation (c.1772C > A; p.Ser591Tyr) in the TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities in different stages of severity among three patients in this family. CONCLUSIONS: This report describes a novel mutation in the TGFBI gene found in three family members affected by different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy; therefore, it could be considered a novel phenotype genotype correlation, which will help in genetic counselling for this family.