A rare homozygous variant in CUL7 gene in two syblings with variable features of 3M syndrome

14. ULUSAL TIBBİ GENETİK KONGRESİ“Uluslararası Katılımlı”, Türkiye, 20 - 22 Kasım 2020

Sinem Kocagil1, Gonca Kılıç Yıldırım2, Sevilhan Artan1

1Department of Medical Genetics, Faculty of Medicine, Eskisehir Osmangazi University

2Department of Pediatrics, Faculty of Medicine, Eskisehir Osmangazi University

3M Syndrome is a rare, autosomal recessive disorder that leads to pre- and postnatal growth failure, facial dysmorphism, joint

hypermobility, delayed bone age, normal intelligence and spesific radiological findings. CUL7, OBSL1, and CCDC8 genes are

known to be responsible in the etiology.

In this study we have evaluated two sisters that present variable clinical features of 3M syndrome. The first sister was 15 years

old and had mesomelic disproportionate short stature, dysmorphic features and pathological skeletal x-ray findings; slender

dysplastic ribs, tall lumbar vertebrae bodies and coxa vara deformity of bilateral hips. The second sister was 11 years old and she

also had mesomelic disproportionate short stature, dysmorphic features and tall lumbar vertebrae bodies at the radiography.

According to these findings 3M syndrome was suspected and CUL7 gene, which is known to play the major role underlying the

syndrome has been sequenced and a ‘‘pathogenic’’ c.362dupT variant in exon 2 at homozygous state leads to a frameshift and

generates a premature termination codon was detected.

We believe that the patients we present will expand the phenotypic spectrum of this rare syndrome and ease to make a

phenotype-genotype association.

Keywords: 3M Syndrome, Rare variants