Combined use of multiplex ligation-dependent probe amplification and automatic sequencing for identification of KAL1 defects in patients with Kallmann syndrome
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Citações na Scopus
11
Tipo de produção
article
Data de publicação
2013
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE INC
Autores
CASTRO, Margaret de
VERSIANI, Beatriz R.
Citação
FERTILITY AND STERILITY, v.100, n.3, p.854-859, 2013
Resumo
Objective: To investigate the role of KAL1 abnormalities in Brazilian patients with Kallmann syndrome. Design: In vitro experiments. Setting: Academic medical center. Patient(s): One hundred fifteen Brazilian patients (98 men) with Kallmann syndrome. Intervention(s): Peripheral blood leukocytes were used to obtain DNA. Main Outcome Measure(s): Direct sequencing and multiplex ligation-dependent probe amplification were used to identify KAL1 abnormalities. Result(s): We identified four KAL1 mutations (p.Met1?, p.Ala33Glyfs, p.Arg257*, and p.Trp462*) and two multiple exon deletions (exons 1-2 and 3-14) in six new male patients. Overall, 17 KAL1 defects (14.8%) were identified in the entire cohort of patients with Kallmann syndrome, including previously studied cases. KAL1-mutated patients presented with a more severe reproductive and nonreproductive phenotype (synkinesia, renal malformations, cryptorchidism, and anatomic olfactory abnormalities) in comparison with patients without KAL1 mutations. Intragenic deletions were one of the most often encountered defects (29.4%). These deletions can be missed by polymerase chain reaction (PCR) due to Yq11.2 KAL1 pseudogene (KALP) spurious amplification. Conclusion(s): These results indicate that intragenic multiexon deletions are one of the most frequent KAL1 abnormalities, which can be more accurately detected by multiplex ligation-dependent probe amplification. In addition, KAL1 sequencing results should be interpreted with caution, and stringency conditions of the PCR reaction should be adjusted to avoid pseudogene amplification. (C) 2013 by American Society for Reproductive Medicine.
Palavras-chave
Kallmann syndrome, KAL1 abnormalities, MLPA, KALP spurious amplification
Referências
- Abreu AP, 2008, J CLIN ENDOCR METAB, V93, P4113, DOI 10.1210/jc.2008-0958
- DELCASTILLO I, 1992, NAT GENET, V2, P305, DOI 10.1038/ng1292-305
- FRANCO B, 1991, NATURE, V353, P529, DOI 10.1038/353529a0
- Hanchate NK, 2012, PLOS GENET, V8, DOI 10.1371/journal.pgen.1002896
- HARDELIN JP, 1993, HUM MOL GENET, V2, P373, DOI 10.1093/hmg/2.4.373
- HARDELIN JP, 1992, P NATL ACAD SCI USA, V89, P8190, DOI 10.1073/pnas.89.17.8190
- HERMANUSSEN M, 1985, CLIN GENET, V28, P106
- Kim HG, 2010, AM J HUM GENET, V87, P465, DOI 10.1016/j.ajhg.2010.08.018
- LEGOUIS R, 1991, CELL, V67, P423, DOI 10.1016/0092-8674(91)90193-3
- Oliveira LMB, 2001, J CLIN ENDOCR METAB, V86, P1532, DOI 10.1210/jc.86.4.1532
- Pedersen-White JR, 2008, MOL HUM REPROD, V14, P367, DOI 10.1093/molehr/gan027
- Pitteloud N, 2002, J CLIN ENDOCR METAB, V87, P152, DOI 10.1210/jc.87.1.152
- Quinton R, 2001, CLIN ENDOCRINOL, V55, P163, DOI 10.1046/j.1365-2265.2001.01277.x
- Ribeiro RS, 2007, EUR J ENDOCRINOL, V156, P285, DOI 10.1530/eje.1.02342
- RUGARLI EI, 1993, NAT GENET, V4, P19, DOI 10.1038/ng0593-19
- Salenave S, 2008, J CLIN ENDOCR METAB, V93, P758, DOI 10.1210/jc.2007-1168
- Seminara SB, 2000, J ENDOCRINOL INVEST, V23, P560
- Silveira LFG, 2010, MOL CELL ENDOCRINOL, V324, P30, DOI 10.1016/j.mce.2010.02.023
- Soderlund D, 2004, J ENDOCRINOL INVEST, V27, P765
- Trarbach EB, 2010, J CLIN ENDOCR METAB, V95, P3491, DOI 10.1210/jc.2010-0176
- Trarbach EB, 2005, J ENDOCRINOL, V187, P361, DOI 10.1677/joe.1.06103
- Trarbach EB, 2004, GENET MOL BIOL, V27, P337, DOI 10.1590/S1415-47572004000300006
- Trarbach EB, 2007, PITUITARY, V10, P381, DOI 10.1007/s11102-007-0061-7
- Trarbach EB, 2006, J CLIN ENDOCR METAB, V91, P4006, DOI 10.1210/jc.2005-2793
- Tsai PS, 2006, NAT CLIN PRACT ENDOC, V2, P160, DOI 10.1038/ncpendmet0119
- Versiani BR, 2007, CLIN ENDOCRINOL, V66, P173, DOI 10.1111/j.1365-2265.2006.02702.x