ESPE Abstracts (2018) 89 P-P2-263

Genetic Investigation of SHORT Stature: A Case Report of Complex Constitutive Rearrangement Involving Chromosome 15

Renata Machado Pintoa,b,c, Lysa Bernardes Minasic,d, Irene Plaza Pintoc,d, Juliana Ferreira da Silvad, Damiana Mirian da Cruz Cunhac,d, Cristiano Luiz Ribeirod, Cláudio Carlos da Silvac,d & Aparecido Divino da Cruzc,d

aFederal University of Goias, Health Science PhD Program, Goiânia, Brazil; bFederal University of Goias, Professor of Pediatrics, Goiânia, Brazil; cPontifical Catholic University of Goiás, Department of Agricultural and Biological Sciences, Genetics Master’s Program, Replicon Research Group, Goiânia, Brazil; dHuman Cytogenetics and Molecular Genetics Laboratory, Secretary of Goias State for Public Health, Goiânia, Brazil

Introduction: Growth is a complex process influenced by several genetic factors both pre and postnatal, in which 80% of the height variation is explained by genetic factors. Nevertheless, the standard medical evaluation of short stature (SS) relies upon physical examination and laboratory parameters and identifies a pathological cause of SS in 1–40% of individuals. Rearrangements affecting chromosome 15 are rare and affected patients show a variety of nonspecific features, including complex congenital malformations, growth deficiency, and developmental delay.

Case report: LDG 1 year 11 months years old girl, first daughter of a non-consanguineous young couple presented to the Pediatric Endocrinology service with a short stature complaint. She was born AGA (2760 g and 48 cm) at 37 weeks of gestation. Physical examination revealed brachydactyly, triangular face, and facial dysmorphisms with prominent forehead, hypertelorism, bulbous nasal tip, long philtrum, thin upper lip, and micrognathism. The height was 71 cm (−4,2 S.D.) weight 7000 g (−3,7 S.D.), cephalic perimeter 43,5 cm (−1,39SD). G-banding analysis was performed, followed by FISH using probes 15q11-13 (SNRPN) for Prader-Willi/Angelman and 15q26.3 for internal control. The karyotype showed a constitutive chromosomal aberration, 46,XX,r(15)[64]/46,XX,r(15)dup(15)[16]/47,XX,+r(15)[5]. FISH analysis confirmed the karyotype results and showed two more different cell lines 46,XX[9]/45,XX,-15[6]. In r(15) was detected the absence of the 15q26.3 signal resulting in a genetic material loss, region that harbor IGF1R gene, wich is responsible for the biological activity of IGF1.

Conclusions: Ring chromosome results from breakage in both arms of a chromosome, with fusion of the points of fracture and loss of the distal fragments. In this context, a ring induces chromosomal instability, which in turn generates a diversity of cell lines harboring different chromosome configurations. In the case described here, we hypothesized that a 46,XX zygote acquired a r(15) leading to the instability subjacent to the other cell lines that had ring duplication, monosomy 15, trisomy 15, which included r(15), most likely due to different approaches to restore balanced genome in the cells, such as trisomy rescue and Uniparental Disomy. Genetic diagnosis in cases of SS is important because it can end the diagnostic workup for the patient, it may alert the clinician to other medical comorbidities for which the patient is at risk, and it is extremely valuable for the genetic counselling