| [PMID]: | 22903559 |
| [Au] Autor: | Jamsheer A; Sowinska A; Trzeciak T; Jamsheer-Bratkowska M; Geppert A; Latos-Bielenska A |
| [Ad] Endereço: | Department of Medical Genetics, University of Medical Sciences, ul. Grunwaldzka 55 paw. 15, 60-352 Poznan, Poland. jamsheer@wp.pl |
| [Ti] Título: | Expanded mutational spectrum of the GLI3 gene substantiates genotype-phenotype correlations. |
| [So] Source: | J Appl Genet;53(4):415-22, 2012 Nov. |
| [Is] ISSN: | 2190-3883 |
| [Cp] País de publicação: | England |
| [La] Idioma: | eng |
| [Ab] Resumo: | Greig cephalopolysyndactyly syndrome (GCPS) and isolated preaxial polydactyly type IV (PPD-IV) are rare autosomal dominant disorders, both caused by mutations in the GLI3 gene. GCPS is mainly characterised by craniofacial abnormalities (macrocephaly/prominent forehead, hypertelorism) and limb malformations, such as PPD-IV, syndactyly and postaxial polydactyly type A or B (PAPA/B). Mutations in the GLI3 gene can also lead to Pallister-Hall syndrome (PHS) and isolated PAPA/B. In this study, we investigated 16 unrelated probands with the clinical diagnosis of GCPS/PPD-IV and found GLI3 mutations in 12 (75%) of them (nine familial and three sporadic cases). We also performed a detailed clinical evaluation of all 12 GLI3-positive families, with a total of 27 patients. The hallmark triad of GCPS (preaxial polydactyly, macrocephaly/prominent forehead, hypertelorism) was present in 14 cases (52%), whereas at least one typical dysmorphic feature was manifested in 17 patients (63%). Upon sequencing of the GLI3 gene, we demonstrated eight novel and two previously reported heterozygous point mutations. We also performed multiplex ligation-dependent probe amplification (MLPA) to screen for intragenic copy number changes and identified heterozygous deletions in the two remaining cases (16.7%). Our findings fully support previous genotype-phenotype correlations, showing that exonic deletions, missense mutations, as well as truncating variants localised out of the middle third of the GLI3 gene result in GCPS/PPD-IV and not PHS. Additionally, our study shows that intragenic GLI3 deletions may account for a significant proportion of GCPS/PPD-IV causative mutations. Therefore, we propose that MLPA or quantitative polymerase chain reaction (qPCR) should be implemented into routine molecular diagnostic of the GLI3 gene. |
| [Mh] Termos MeSH primário: |
Acrocefalossindactilia/genética
Estudos de Associação Genética/métodos
Fatores de Transcrição Kruppel-Like/genética
Proteínas do Tecido Nervoso/genética
Mutação Puntual
Polidactilia/genética
|
| [Mh] Termos MeSH secundário: |
Acrocefalossindactilia/diagnóstico
Adolescente
Adulto
Criança
Pré-Escolar
Variações do Número de Cópias de DNA
Testes Genéticos/métodos
Heterozigoto
Seres Humanos
Lactente
Fatores de Transcrição Kruppel-Like/metabolismo
Masculino
Meia-Idade
Mutação de Sentido Incorreto
Proteínas do Tecido Nervoso/metabolismo
Síndrome de Pallister-Hall/genética
Linhagem
Polidactilia/diagnóstico
Reação em Cadeia da Polimerase em Tempo Real/métodos
Polegar/anormalidades
Adulto Jovem
Proteína Gli3 com Dedos de Zinco
|
| [Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (GLI3 protein, human); 0 (Kruppel-Like Transcription Factors); 0 (Nerve Tissue Proteins); 0 (Zinc Finger Protein Gli3) |
| [Em] Mês de entrada: | 1303 |
| [Cu] Atualização por classe: | 171116 |
[Lr] Data última revisão:
| 171116 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 120821 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1007/s13353-012-0109-x |
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