ALX4 dysfunction disrupts craniofacial and epidermal development
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Tarih
2009
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Oxford Univ Press
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Genetic control of craniofacial morphogenesis requires a complex interaction of numerous genes encoding factors essential for patterning and differentiation. We present two Turkish families with a new autosomal recessive frontofacial dysostosis syndrome characterized by total alopecia, a large skull defect, coronal craniosynostosis, hypertelorism, severely depressed nasal bridge and ridge, bifid nasal tip, hypogonadism, callosal body agenesis and mental retardation. Using homozygosity mapping, we mapped the entity to chromosome 11p11.2-q12.3 and subsequently identified a homozygous c.793C -> T nonsense mutation in the human ortholog of the mouse aristaless-like homeobox 4 (ALX4) gene. This mutation is predicted to result in a premature stop codon (p.R265X) of ALX4 truncating 146 amino acids of the protein including a part of the highly conserved homeodomain and the C-terminal paired tail domain. Although the RNA is stable and not degraded by nonsense-mediated RNA decay, the mutant protein is likely to be non-functional. In a skin biopsy of an affected individual, we observed a hypomorphic interfollicular epidermis with reduced suprabasal layers associated with impaired interfollicular epidermal differentiation. Hair follicle-like structures were present but showed altered differentiation. Our data indicate that ALX4 plays a critical role both in craniofacial development as in skin and hair follicle development in human.
Açıklama
Akarsu, Nurten/0000-0001-5432-0032; Alanay, Yasemin/0000-0003-0683-9731
Anahtar Kelimeler
Kaynak
Human Molecular Genetics
WoS Q Değeri
Q1
Scopus Q Değeri
Q2
Cilt
18
Sayı
22
Künye
Kayserili, H., Uz, E., Niessen, C., Vargel, I., Alanay, Y., Tuncbilek, G., Yigit, G., Uyguner, O., Candan, S., Okur, H., Kaygin, S., Balci, S., Mavili, E., Alikasifoglu, M., Haase, I., Wollnik, B., & Akarsu, N. A. (2009). ALX4 dysfunction disrupts craniofacial and epidermal development. Human molecular genetics, 18(22), 4357–4366. https://doi.org/10.1093/hmg/ddp391
