Brittle Cornea Syndrome Associated with a Missense Mutation in the Zinc-Finger 469 Gene

Anne Elisabeth Christensen; Per Morten Knappskog; Marit Midtbø; Clara Gram Gjesdal; Jonas Mengel-From; Niels Morling; Eyvind Rodahl; Helge Boman

doi:10.1167/iovs.09-4251

Brittle Cornea Syndrome Associated with a Missense Mutation in the Zinc-Finger 469 Gene

Anne Elisabeth Christensen, Per Morten Knappskog, Marit Midtbø, Clara Gram Gjesdal, Jonas Mengel-From, Niels Morling, Eyvind Rodahl, Helge Boman

34 Citations (Scopus)

Abstract

PURPOSE. To investigate the diverse clinical manifestations, identify the causative mutation and explain the association with red hair in a family with brittle cornea syndrome (BCS). METHODS. Eight family members in three generations underwent ophthalmic, dental, and general medical examinations, including radiologic examination of the spine. Bone mineral density (BMD) and serum levels of vitamin D, parathyroid hormone, and biochemical markers for bone turnover were measured. Skin biopsies were examined by light and transmission electron microscopy. Molecular genetic studies included homozygosity mapping with SNP markers, DNA sequencing, and MC1R genotyping. RESULTS. At 42 and 48 years of age, respectively, both affected individuals were blind due to retinal detachment and secondary glaucoma. They had extremely thin and bulging corneas, velvety skin, chestnut colored hair, scoliosis, reduced BMD, dental anomalies, hearing loss, and minor cardiac defects. The morphologies of the skin biopsies were normal except that in some areas slightly thinner collagen fibrils were seen in one of the affected individuals. Molecular genetic analysis revealed a novel missense mutation of ZNF469, c.10016G>A, that was predicted to affect the fourth of the five zinc finger domains of ZNF469 by changing the first cysteine to a tyrosine (p.Cys3339Tyr). Both affected individuals were homozygous for the common red hair variant R151C at the MC1R locus. CONCLUSIONS. BCS is a disorder that affects a variety of connective tissues. Reduced BMD and atypical dental crown morphology have not been reported previously. The results confirm that BCS is associated with mutations in ZNF469. The association with red hair in some individuals with BCS is likely to occur by chance.

Original language	English
Journal	Investigative Ophthalmology & Visual Science
Volume	51
Issue number	1
Pages (from-to)	47-52
Number of pages	6
ISSN	0146-0404
DOIs	https://doi.org/10.1167/iovs.09-4251
Publication status	Published - Jan 2010

Access to Document

10.1167/iovs.09-4251

https://iovs.arvojournals.org/data/journals/iovs/933452/z7g00110000047.pdf

Cite this

@article{6d99a5508b1a11de8bc9000ea68e967b,

title = "Brittle Cornea Syndrome Associated with a Missense Mutation in the Zinc-Finger 469 Gene",

abstract = "PURPOSE. To investigate the diverse clinical manifestations, identify the causative mutation and explain the association with red hair in a family with brittle cornea syndrome (BCS). METHODS. Eight family members in three generations underwent ophthalmic, dental, and general medical examinations, including radiologic examination of the spine. Bone mineral density (BMD) and serum levels of vitamin D, parathyroid hormone, and biochemical markers for bone turnover were measured. Skin biopsies were examined by light and transmission electron microscopy. Molecular genetic studies included homozygosity mapping with SNP markers, DNA sequencing, and MC1R genotyping. RESULTS. At 42 and 48 years of age, respectively, both affected individuals were blind due to retinal detachment and secondary glaucoma. They had extremely thin and bulging corneas, velvety skin, chestnut colored hair, scoliosis, reduced BMD, dental anomalies, hearing loss, and minor cardiac defects. The morphologies of the skin biopsies were normal except that in some areas slightly thinner collagen fibrils were seen in one of the affected individuals. Molecular genetic analysis revealed a novel missense mutation of ZNF469, c.10016G>A, that was predicted to affect the fourth of the five zinc finger domains of ZNF469 by changing the first cysteine to a tyrosine (p.Cys3339Tyr). Both affected individuals were homozygous for the common red hair variant R151C at the MC1R locus. CONCLUSIONS. BCS is a disorder that affects a variety of connective tissues. Reduced BMD and atypical dental crown morphology have not been reported previously. The results confirm that BCS is associated with mutations in ZNF469. The association with red hair in some individuals with BCS is likely to occur by chance.",

author = "Christensen, {Anne Elisabeth} and Knappskog, {Per Morten} and Marit Midtb{\o} and Gjesdal, {Clara Gram} and Jonas Mengel-From and Niels Morling and Eyvind Rodahl and Helge Boman",

note = "170809 Epub ahead of print. Ingen sidereferencer.",

year = "2010",

month = jan,

doi = "10.1167/iovs.09-4251",

language = "English",

volume = "51",

pages = "47--52",

journal = "Investigative Ophthalmology & Visual Science",

issn = "0146-0404",

publisher = "Association for Research in Vision and Ophthalmology",

number = "1",

}

TY - JOUR

T1 - Brittle Cornea Syndrome Associated with a Missense Mutation in the Zinc-Finger 469 Gene

AU - Christensen, Anne Elisabeth

AU - Knappskog, Per Morten

AU - Midtbø, Marit

AU - Gjesdal, Clara Gram

AU - Mengel-From, Jonas

AU - Morling, Niels

AU - Rodahl, Eyvind

AU - Boman, Helge

N1 - 170809 Epub ahead of print. Ingen sidereferencer.

PY - 2010/1

Y1 - 2010/1

N2 - PURPOSE. To investigate the diverse clinical manifestations, identify the causative mutation and explain the association with red hair in a family with brittle cornea syndrome (BCS). METHODS. Eight family members in three generations underwent ophthalmic, dental, and general medical examinations, including radiologic examination of the spine. Bone mineral density (BMD) and serum levels of vitamin D, parathyroid hormone, and biochemical markers for bone turnover were measured. Skin biopsies were examined by light and transmission electron microscopy. Molecular genetic studies included homozygosity mapping with SNP markers, DNA sequencing, and MC1R genotyping. RESULTS. At 42 and 48 years of age, respectively, both affected individuals were blind due to retinal detachment and secondary glaucoma. They had extremely thin and bulging corneas, velvety skin, chestnut colored hair, scoliosis, reduced BMD, dental anomalies, hearing loss, and minor cardiac defects. The morphologies of the skin biopsies were normal except that in some areas slightly thinner collagen fibrils were seen in one of the affected individuals. Molecular genetic analysis revealed a novel missense mutation of ZNF469, c.10016G>A, that was predicted to affect the fourth of the five zinc finger domains of ZNF469 by changing the first cysteine to a tyrosine (p.Cys3339Tyr). Both affected individuals were homozygous for the common red hair variant R151C at the MC1R locus. CONCLUSIONS. BCS is a disorder that affects a variety of connective tissues. Reduced BMD and atypical dental crown morphology have not been reported previously. The results confirm that BCS is associated with mutations in ZNF469. The association with red hair in some individuals with BCS is likely to occur by chance.

AB - PURPOSE. To investigate the diverse clinical manifestations, identify the causative mutation and explain the association with red hair in a family with brittle cornea syndrome (BCS). METHODS. Eight family members in three generations underwent ophthalmic, dental, and general medical examinations, including radiologic examination of the spine. Bone mineral density (BMD) and serum levels of vitamin D, parathyroid hormone, and biochemical markers for bone turnover were measured. Skin biopsies were examined by light and transmission electron microscopy. Molecular genetic studies included homozygosity mapping with SNP markers, DNA sequencing, and MC1R genotyping. RESULTS. At 42 and 48 years of age, respectively, both affected individuals were blind due to retinal detachment and secondary glaucoma. They had extremely thin and bulging corneas, velvety skin, chestnut colored hair, scoliosis, reduced BMD, dental anomalies, hearing loss, and minor cardiac defects. The morphologies of the skin biopsies were normal except that in some areas slightly thinner collagen fibrils were seen in one of the affected individuals. Molecular genetic analysis revealed a novel missense mutation of ZNF469, c.10016G>A, that was predicted to affect the fourth of the five zinc finger domains of ZNF469 by changing the first cysteine to a tyrosine (p.Cys3339Tyr). Both affected individuals were homozygous for the common red hair variant R151C at the MC1R locus. CONCLUSIONS. BCS is a disorder that affects a variety of connective tissues. Reduced BMD and atypical dental crown morphology have not been reported previously. The results confirm that BCS is associated with mutations in ZNF469. The association with red hair in some individuals with BCS is likely to occur by chance.

U2 - 10.1167/iovs.09-4251

DO - 10.1167/iovs.09-4251

M3 - Journal article

C2 - 19661234

SN - 0146-0404

VL - 51

SP - 47

EP - 52

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

IS - 1

ER -

Brittle Cornea Syndrome Associated with a Missense Mutation in the Zinc-Finger 469 Gene

Abstract

Access to Document

Fingerprint

Cite this