Confirmation of the colobomatous macrophthalmia with microcornea syndrome: Report of another family

Pallotta, R; Fusilli, Paola; Sabatino, Giuseppe; Verrotti, Alberto; Chiarelli, Francesco

doi:10.1002/(sici)1096-8628(19980319)76:3<252::aid-ajmg9>3.0.co;2-s

Cited by 13 publications

(5 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additional associations are increased intraocular pressure, shallow anterior chamber depth and mild cornea plana. The MACOM phenotype has originally been described in an autosomal dominant, 2-generation family with 4 affected individuals (1) and successively in a 4-generation family with 4 affected individuals (2) and in a large 3-generation Turkish family with 13 affected individuals (3). MACOM syndrome seems to be fully penetrant in the reported families, but variable expressivity of the phenotype has been observed, e.g.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CRIM1 haploinsufficiency causes defects in eye development in human and mouse

Beleggia¹,

Li²,

Fan³

et al. 2015

Human Molecular Genetics

View full text Add to dashboard Cite

Colobomatous macrophthalmia with microcornea syndrome (MACOM, Online Mendelian Inheritance in Man (OMIM) 602499) is an autosomal dominantly inherited malformation of the eye, which is characterized by microcornea with increased axial length, coloboma of the iris and of the optic disc, and severe myopia. We performed whole-exome sequencing (WES) in two affected individuals from the 2p23-p16-linked MACOM family, which includes 13 affected individuals in 3 generations. As no shared novel variation was found on the linked haplotype, we performed copy number variation (CNV) analysis by comparing the coverage of all exons in the WES data sets of the 2 patients with the coverage of 26 control exomes. We identified a heterozygous deletion predicted to span 22 kb including exons 14-17 of CRIM1 (cysteine-rich transmembrane bone morphogenetic protein (BMP) regulator 1). Quantitative PCR (qPCR) analysis confirmed the deletion, which was present in 11 affected individuals. Split-read analysis of WES data followed by breakpoint PCR and Sanger sequencing determined both breakpoints flanked by a 4-bp microhomology (CTTG). In the mouse, Crim1 is a growth-factor-binding protein with pleiotropic roles in the development of multiple organs, including the eye. To investigate the role of Crim1 during eye development in mice, we crossed a Crim1(flox) mouse line with the Ap2α-cre mouse line, which expresses Cre in the head surface ectoderm. Strikingly, we observed alterations of eye development in homozygous mice leading to severe anatomical and morphological changes overlapping with the anomalies observed in MACOM patients. Taken together, these findings identify CRIM1 as the causative gene for MACOM syndrome and emphasize the importance of CRIM1 in eye development.

show abstract

Section: Introductionmentioning

confidence: 99%

“…unilateral presentation (1) and variability in the position and extent of the coloboma, different degrees of corneal diameter reduction and variable severity of macrophthalmia. The severe myopia present in the affected individuals is thought to be secondary to the staphyloma and increased axial length (2).…”

Section: Introductionmentioning

confidence: 99%

CRIM1 haploinsufficiency causes defects in eye development in human and mouse

Beleggia¹,

Li²,

Fan³

et al. 2015

Human Molecular Genetics

View full text Add to dashboard Cite

show abstract

“…Aniridia, an uncommon congenital defect of the iris morphology, is mainly transmitted as an autosomal dominant trait 1. Being a bilateral, panocular disorder, the cornea (microcornea, corneal opacity), anterior chamber angle (glaucoma), lens (cataract, subluxation), retina (foveal hypoplasia) and optic nerve (nerve hypoplasia) can also be involved 1.…”

mentioning

confidence: 99%

“…Being a bilateral, panocular disorder, the cornea (microcornea, corneal opacity), anterior chamber angle (glaucoma), lens (cataract, subluxation), retina (foveal hypoplasia) and optic nerve (nerve hypoplasia) can also be involved 1. We describe unique anterior and posterior segment anomalies in twin sisters and three children of one of the twins [Fig.…”

mentioning

confidence: 99%

Inherited partial aniridia, microcornea with high myopia and Bergmeister′s papilla: A new phenotypic expression

Naithani

Sinha

Gupta

2008

Indian J Ophthalmol

View full text Add to dashboard Cite

show abstract

“…Other associated findings are mild cornea plana, iridocorneal angle abnormalities with increased intraocular pressure, and relatively shallow anterior chamber depth [Toker et al, 2003]. Bateman described this syndrome in a two‐generation family with four affected members (a woman, her monozygotic twin, and her twin's two sons); subsequently, four additional patients with similar ocular findings were reported in an Italian family [Pallotta et al, 1998]. More recently, we have identified colobomatous macrophthalmia with microcornea syndrome in a Turkish family with 13 affected individuals, 11 living and 2 deceased [Toker et al, 2003].…”

Section: Introductionmentioning

confidence: 88%

Colobomatous macrophthalmia with microcornea syndrome maps to the 2p23‐p16 region

Elçioğlu

Akin

Toker

et al. 2007

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Colobomatous macrophthalmia with microcornea syndrome (OMIM 602499) is a rare, autosomal dominant malformation characterized by microcornea, uveal coloboma, axial enlargement of the globe, and myopia. Using what is currently the largest described pedigree and candidate localization approach, we first excluded the candidate genes PAX2, PAX3, PAX6, and PAX9. Subsequently, the chromosome 14q24 region containing the CHX10, SIX1, and SIX4 genes were also excluded. Positive LOD scores were obtained with the DNA markers selected from the 2p23-p16 region. A maximum pairwise LOD score of 3.61 (Theta = 0) was noted with the DNA marker D2S1788. Haplotype analysis positioned the locus between DNA markers D2S2263 and D2S1352 within a 22 Mb physical interval. This region contains major candidate genes, such as SIX2, SIX3, and CYP1B1; however, mutation analysis did not identify a causative mutation in these genes. Macrophthalmia, colobomatous, with microcornea (MACOM) is proposed as the gene symbol for this malformation linked to 2p23-p16.

show abstract

Confirmation of the colobomatous macrophthalmia with microcornea syndrome: Report of another family

Cited by 13 publications

References 12 publications

CRIM1 haploinsufficiency causes defects in eye development in human and mouse

CRIM1 haploinsufficiency causes defects in eye development in human and mouse

Inherited partial aniridia, microcornea with high myopia and Bergmeister′s papilla: A new phenotypic expression

Colobomatous macrophthalmia with microcornea syndrome maps to the 2p23‐p16 region

Contact Info

Product

Resources

About