title: SMOC1 is essential for ocular and limb development in humans and mice.
abstract: Microphthalmia with limb anomalies (MLA) is a rare autosomal-recessive disorder, presenting with anophthalmia or microphthalmia and hand and/or foot malformation. We mapped the MLA locus to 14q24 and successfully identified three homozygous (one nonsense and two splice site) mutations in the SPARC (secreted protein acidic and rich in cysteine)-related modular calcium binding 1 (SMOC1) in three families. Smoc1 is expressed in the developing optic stalk, ventral optic cup, and limbs of mouse embryos. Smoc1 null mice recapitulated MLA phenotypes, including aplasia or hypoplasia of optic nerves, hypoplastic fibula and bowed tibia, and syndactyly in limbs. A thinned and irregular ganglion cell layer and atrophy of the anteroventral part of the retina were also observed. Soft tissue syndactyly, resulting from inhibited apoptosis, was related to disturbed expression of genes involved in BMP signaling in the interdigital mesenchyme. Our findings indicate that SMOC1/Smoc1 is essential for ocular and limb development in both humans and mice.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Ippei
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authors.lastname: Okada
authors.forename: Haruka
authors.initials: H
authors.lastname: Hamanoue
authors.forename: Koji
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authors.lastname: Terada
authors.forename: Takaya
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authors.lastname: Tohma
authors.forename: Andre
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authors.forename: Joelle
authors.initials: J
authors.lastname: Abou-Ghoch
authors.forename: Nadine
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authors.lastname: Jalkh
authors.forename: Ozgur
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authors.lastname: Cogulu
authors.forename: Ferda
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authors.lastname: Ozkinay
authors.forename: Kyoji
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authors.lastname: Horie
authors.forename: Junji
authors.initials: J
authors.lastname: Takeda
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Furuichi
authors.forename: Shiro
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authors.lastname: Ikegawa
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Satoko
authors.initials: S
authors.lastname: Miyatake
authors.forename: Akira
authors.initials: A
authors.lastname: Nishimura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizuguchi
authors.forename: Norio
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authors.lastname: Niikawa
authors.forename: Fumiki
authors.initials: F
authors.lastname: Hirahara
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kaname
authors.forename: Koh-Ichiro
authors.initials: K
authors.lastname: Yoshiura
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Doi
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furukawa
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
mesh_terms: D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D018389:Codon, Nonsense / Q000235:genetics; D005121:Extremities / Q000254:growth & development; D005123:Eye / Q000254:growth & development; D005808:Genes, Recessive; D056426:Genetic Loci; D006801:Humans; D017880:Limb Deformities, Congenital / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008850:Microphthalmos / Q000235:genetics*; D008969:Molecular Sequence Data; D009900:Optic Nerve / Q000002:abnormalities; D015676:Osteonectin / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics; D014849:Waardenburg Syndrome / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D015676:Osteonectin; C524549:SMOC-1 protein, mouse; C468135:SMOC1 protein, human