Alternative titles; symbols
ORPHA: 158676, 595356; DO: 0080086;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3p21.31 | Nail disorder, nonsyndromic congenital, 8 | 607523 | Autosomal dominant | 3 | COL7A1 | 120120 |
A number sign (#) is used with this entry because nonsyndromic congenital nail disorder-8 (NDNC8) is caused by heterozygous mutation in the COL7A1 gene (120120) on chromosome 3p21.
This form of isolated toenail dystrophy has been found to segregate as an autosomal dominant trait in families in which another member has the autosomal recessive skin disorder dystrophic epidermolysis bullosa (226600) or transient bullous dermolysis of the newborn (131705), the features of which include dystrophic nails. The nail changes in isolated toenail dystrophy are most severe in the great toes and consist of the nail plate being buried in the nail bed with a deformed and narrow free edge (summary by Sato-Matsumura et al., 2002). This form of toenail dystrophy is referred to here as nonsyndromic congenital nail disorder-8 (NDNC8).
For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
Sato-Matsumura et al. (2002) reported 2 unrelated Japanese families in which isolated toenail deformity was inherited in an autosomal dominant manner. The nail plates of the toes were buried in the nail bed, and the free edge of the toenail was deformed and narrow. The deformity was most severe on the big toes. No family members with the toenail deformity had a dermatologic disorder or skin fragility. Both probands had a child with recessive dystrophic epidermolysis bullosa (RDEB; 226600).
The transmission pattern of NDNC8 in the family reported by Hammami-Hauasli et al. (1998) was consistent with autosomal dominant inheritance.
In the family of a 14-month-old girl with transient bullous dermolysis of the newborn (TBDN; 131705) due to compound heterozygosity for mutations in COL7A1 (G2251E, 120120.0014 and G1519D, 120120.0015), Hammami-Hauasli et al. (1998) observed that the mother, a heterozygous carrier of the G2251E mutation, had toenail dystrophy but no skin lesions. The maternal great-grandmother was reported to have had dystrophy of some fingernails since childhood, but never had skin blistering. The father, who carried the G1519D mutation, was clinically unaffected.
Shimizu et al. (1999) studied the family of a 10-year-old Japanese girl, originally reported by Hatta et al. (1995), who presented with an unusual epidermolysis bullosa dystrophica (DEB) phenotype that resembled transient bullous dermolysis of the newborn (TBDN; 131705). At age 10 years, she had moderately severe DEB and was found to be compound heterozygous for missense mutations in the COL7A1 gene, G2316R (120120.0042) and G2287R (120120.0023). Although her mother was described as clinically unaffected in the original report, reexamination of family members revealed the presence of mild nail dystrophy restricted to the great toenails, without skin fragility, in all heterozygous carriers of the G2287R mutation, including the proband's mother, maternal uncle, and maternal grandmother. Individuals heterozygous for the paternal G2316R mutation were clinically unaffected.
Sato-Matsumura et al. (2002) examined 2 unrelated Japanese families with recessive dystrophic epidermolysis bullosa (RDEB) for mutations in the COL7A1 gene and identified family members with dystrophic changes limited to the toenails but without skin fragility who were heterozygous for the glycine substitutions G1595R (120120.0024) and G1815R (120120.0025), respectively. The isolated toenail dystrophy was inherited in an autosomal dominant manner. The patients with RDEB in each family were compound heterozygous for 1 of these mutations, respectively, in combination with a nonsense or frameshift mutation in COL7A1. These results supported the idea that certain glycine substitutions in the collagenous domain of COL7A1 cause a limited nail deformity and that these alleles can also contribute to variable degrees of skin fragility when present in combination with nonsense or frameshift mutations in COL7A1.
Hammami-Hauasli, N., Raghunath, M., Kuster, W., Bruckner-Tuderman, L. Transient bullous dermolysis of the newborn associated with compound heterozygosity for recessive and dominant COL7A1 mutations. J. Invest. Derm. 111: 1214-1219, 1998. [PubMed: 9856844] [Full Text: https://doi.org/10.1046/j.1523-1747.1998.00394.x]
Hatta, N., Takata, M., Shimizu, H. Spontaneous disappearance of intraepidermal type VII collagen in a patient with dystrophic epidermolysis bullosa. Brit. J. Derm. 133: 619-624, 1995. [PubMed: 7577595] [Full Text: https://doi.org/10.1111/j.1365-2133.1995.tb02716.x]
Sato-Matsumura, K. C., Yasukawa, K., Tomita, Y., Shimizu, H. Toenail dystrophy with COL7A1 glycine substitution mutations segregates as an autosomal dominant trait in 2 families with dystrophic epidermolysis bullosa. Arch. Derm. 138: 269-271, 2002. [PubMed: 11843659] [Full Text: https://doi.org/10.1001/archderm.138.2.269]
Shimizu, H., Hammami-Hauasli, N., Hatta, N., Nishikawa, T., Bruckner-Tuderman, L. Compound heterozygosity for silent and dominant glycine substitution mutations in COL7A1 leads to a marked transient intracytoplasmic retention of procollagen VII and a moderately severe dystrophic epidermolysis bullosa phenotype. J. Invest. Derm. 113: 419-421, 1999. [PubMed: 10469344] [Full Text: https://doi.org/10.1046/j.1523-1747.1999.00713.x]