Targeted Panel Gene Sequencing for Identification of Genetic Etiology of 46,XY Disorders of Sex Development.

Aghayeva A., Turan H., Toksoy G. , Dağdeviren Çakır A., Berkay E., Güneş N., ...More

58th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE), Vienna, Austria, 19 - 21 September 2019, vol.91, no.1, pp.361

  • Publication Type: Conference Paper / Summary Text
  • Volume: 91
  • Doi Number: 10.1159/000501868
  • City: Vienna
  • Country: Austria
  • Page Numbers: pp.361


Introduction: Congenital adrenal hyperplasia (CAH) is an autosomal

recessively transmitted disease and 95% of CAH cases are

due to 21-hydroxylase deficiency (21-OHD). There are more than

100 mutations that cause CAH due to 21-OHD and the clinical expression

of the disease is reported to correlate with mutated alleles.

The aim: The aim of this study was to investigate responsible

mutations and then to evaluate genotype-phenotype relationship

in CAH patients with 21-OHD.

Methods: Mutations were firstly investigated by sequence

analysis by Sanger method; when needed Multiplex Ligation-dependent

Probe Amplification (MLPA) technique was applied. Mutations

were grouped as of group 0, A, B or C and compared with

the expected clinical phenotype i.e. Group 0: Salt wasting (SW),

Group A: SW, Group B: Simple virilizing (SV), Group C: Nonclassical

(NC) and positive predictive value (ppv) was determined for

the different groups (1).

Subjects: Genotype was investigated in 40 cases with 21-OHD

(33 classical, 7 nonclassical).

Results: Responsible mutations were determined in 37

of the cases (n:15 SW, n:15 SV, n:7 NC). The rate of parental

consanguinity was 43.2%. In 4 compound heterozygotes genotypes

were determined after the genotyping of parents. In 11 cases only

Sanger method, in 26 cases Sanger and MLPA methods were used.

Mutations were identified in 73 alleles from 37 cases (mutation

only in one allele in one case: Deletion/Not detected). The most

common mutation was IVS2-13A/C>G (28.3%), followed by

p.I172N mutation (17.5%) and large gene deletions (14.7%). In

addition, heterozygosity for p.Y59N mutation which has not been

previously reported in our region and a higher rate (10.8%) for the

p.V281L mutation than that reported before was found.