Investigation of Genetic Etiology of Short Stature

14th European Cytogenomics Conference , Montpellier, Fransa, 1 - 04 Temmuz 2023, ss.50

Slowing down or pausing growth often indicates a

health problem in the child. The main criteria of short

stature are the third height percentile, growth rate

below the 25th percentile, height 8.5 cm shorter than

the expected one, and bone age older than that of

chronological age (>2 SD). Medical history, physical

examination, and laboratory tests are of great

importance in the investigation of short stature, and

these procedures significantly contribute to eluc-

idating etiologic causes.

Short stature is divided into two categories, clinically

pathological and non-pathological, divided into

subgroups related to genetic causes: chromosomal,

single gene, and multifactorial factors.

This study evaluated the genetic etiology of 189

clinically diagnosed short-stature patients with

unknown underlying causes using cytogenetic and

molecular tests to elucidate the genetic etiology.

Patients with normal karyotypes were included in the

analysis of 10 genes (GH1, GHR, GHRH, GHSR,

IGF1, IGF1R, IGFALS, IGFBP3, SHOX, and

STAT5B) which was carried out on the Ion Torrent

platform. Mutations thought to have clinical impor-

tance were confirmed by Sanger sequencing, and

family studies were used for further investigation.

In five cases, significant mutations (BMP4, GHR,

IGSF1, LHX4, and PROKR2) were identified, only

one of which was previously reported. Three muta-

tions were also detected in healthy family members.

This panel of short stature-associated genes was

designed for the first time in Turkey. Its results are

expected to elucidate genetic factors that play a role in

the etiology of this phenotype, reveal genotype-

phenotype correlations, and contribute to personalized

genetic counseling. But, since short stature has a broad

genetic background, we think a gene panel is

insufficient. Using whole-exome or whole-genome

sequencing, the proper approach would be to

investigate index individuals, their parents, and

healthy controls.