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Novel genotype in two siblings with 5-α-reductase 2 deficiency: Different clinical course due to the time of diagnosis

M Kocova
M Kocova
, 
D Plaseska-Karanfilska
D Plaseska-Karanfilska
, 
P Noveski
P Noveski
 oraz 
M Kuzmanovska
M Kuzmanovska
   | 21 gru 2019
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Article Category: Case Report
Data publikacji: 21 gru 2019
Zakres stron: 69 - 76
DOI: https://doi.org/10.2478/bjmg-2019-0022
Słowa kluczowe
© 2019 Kocova M, Plaseska-Karanfilska D, Noveski P, Kuzmanovska M, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1

Physical appearance of patients. A and B) implanted breasts and genital appearance in Patient 1 at age 21. C and D) muscular body and genital appearance of Patient 2 before surgery.
Physical appearance of patients. A and B) implanted breasts and genital appearance in Patient 1 at age 21. C and D) muscular body and genital appearance of Patient 2 before surgery.

Figure 2

A) Electropherograms of Sanger sequencing analysis of SRD5A2 exon 1 in the three siblings and parents: affected siblings (Patients 1 and 2) are hemizygous for the pathogenic c. 146 C>A mutation. Healthy sibling (Patient 3) is heterozygous for the benign c.145 G>A mutation. Mother is a carrier of the pathogenic c.146C>A mutation and father is hemizygous for the benign c. 145 G>A. B) Results from the MLPA analysis using P334-A3 Gonadal Development Disorder kit (MRC-Holland). Two affected siblings and the father are heterozygous for the deletion in exon 1 of the gene; the healthy sibling and the mother are without aberrations in the analyzed genes. Blue and red lines represent 1.3 and 0.7 final ratio of the intensity signal, respectively.
A) Electropherograms of Sanger sequencing analysis of SRD5A2 exon 1 in the three siblings and parents: affected siblings (Patients 1 and 2) are hemizygous for the pathogenic c. 146 C>A mutation. Healthy sibling (Patient 3) is heterozygous for the benign c.145 G>A mutation. Mother is a carrier of the pathogenic c.146C>A mutation and father is hemizygous for the benign c. 145 G>A. B) Results from the MLPA analysis using P334-A3 Gonadal Development Disorder kit (MRC-Holland). Two affected siblings and the father are heterozygous for the deletion in exon 1 of the gene; the healthy sibling and the mother are without aberrations in the analyzed genes. Blue and red lines represent 1.3 and 0.7 final ratio of the intensity signal, respectively.

Figure 3

A) Results from the real-time PCR analysis for the approximate determination of the deletion breakpoints. The first three primers (from rtPCR_1 to rtPCR_3) showed diploid state (two copies of the targeted sequence), while the remaining five primers (from rtPCR_4 to rtPCR_8) showed haploid state (one copy of the amplified sequence) in the affected sibling and the father as compared to a normal healthy male sample used as reference. B) Graphical presentation of the targeted sequences by MLPA and realtime PCR analysis with the use of the UCSC genome browser. Besides custom tracks (MLPA-P334 Gonadal and SRD5A2 realtime PCR primers), the UCSC Genes, RepeatMasker and Agilent Arrays tracks are shown. In the custom tracks, the sequences colored red are those deleted (only one copy) in the father and the two affected siblings, while sequences colored green in the SRD5A2 realtime PCR primers track are undeleted (present in two copies). The deletion breakpoint from the 3’ side (intron 1) is between SRD5A2_rtPCR_3 and SRD5A2_ rtPCR_4 primers, while from the 5’ side (before the SRD5A2 gene) is undetermined. There is increased complexity of the region upstream of the SRD5A2 gene as shown by sequences annotated with RepeatMasker and lack of probes in 40 and 30 kb untargeted regions in the Agilent 4 × 180K and Agilent 1 × 1M arrays, respectively.
A) Results from the real-time PCR analysis for the approximate determination of the deletion breakpoints. The first three primers (from rtPCR_1 to rtPCR_3) showed diploid state (two copies of the targeted sequence), while the remaining five primers (from rtPCR_4 to rtPCR_8) showed haploid state (one copy of the amplified sequence) in the affected sibling and the father as compared to a normal healthy male sample used as reference. B) Graphical presentation of the targeted sequences by MLPA and realtime PCR analysis with the use of the UCSC genome browser. Besides custom tracks (MLPA-P334 Gonadal and SRD5A2 realtime PCR primers), the UCSC Genes, RepeatMasker and Agilent Arrays tracks are shown. In the custom tracks, the sequences colored red are those deleted (only one copy) in the father and the two affected siblings, while sequences colored green in the SRD5A2 realtime PCR primers track are undeleted (present in two copies). The deletion breakpoint from the 3’ side (intron 1) is between SRD5A2_rtPCR_3 and SRD5A2_ rtPCR_4 primers, while from the 5’ side (before the SRD5A2 gene) is undetermined. There is increased complexity of the region upstream of the SRD5A2 gene as shown by sequences annotated with RepeatMasker and lack of probes in 40 and 30 kb untargeted regions in the Agilent 4 × 180K and Agilent 1 × 1M arrays, respectively.
eISSN:
1311-0160
Język:
Angielski
Częstotliwość wydawania:
2 razy w roku
Dziedziny czasopisma:
Medicine, Basic Medical Science, other
Kanał RSS czasopisma