Ichthyosis, Congenital, Autosomal Recessive 13

A number sign (#) is used with this entry because of evidence that autosomal recessive congenital ichthyosis-13 (ARCI13) is caused by homozygous mutation in the SDR9C7 gene (609769) on chromosome 12q13.

For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300).

Clinical Features

Shigehara et al. (2016) studied affected individuals from 3 consanguineous Lebanese families with congenital ichthyosis, who exhibited large erythematous scales over the entire body, particularly the torso, with hyperkeratosis of the elbows and knees. The skin lesions were present at birth, and severity decreased with age. About two-thirds of the patients showed sparing of the face and scalp. Most patients had palmoplantar hyperkeratosis and persistent fungal skin infections, and about half of the patients had onychomycosis. Histologic analysis of affected skin showed mild hypergranulosis and marked hyperkeratosis of the epidermis, consistent with lamellar ichthyosis.

Karim et al. (2017) reported 3 Pakistani sibs who were born encased in collodion membranes that later transformed into generalized nonerythematous scales. Examination showed fine white scales covering upper limbs and trunk, large polygonal brownish scales on the lower limbs, mild facial involvement sparing the scalp, and pronounced hyperlinearity and hyperkeratosis on palms, soles, and dorsal surfaces of hands and feet. Onychomycosis was suspected based on the general appearance of nails, particularly of the toenails. The authors noted that the sibs in this family were more severely affected than the previously reported Lebanese patients, who did not harbor dark brown scales and showed improvement with age.

Mapping

In 3 consanguineous Lebanese families with congenital ichthyosis that did not show linkage to any of the known ichthyosis-associated genes, Shigehara et al. (2016) identified a linkage interval on chromosome 12q13-q14, which recombination events limited to a 9.47-Mb region flanked by markers D12S96 and MON2-MS1. The authors noted that this interval did not overlap with the ARCI7 locus (615022) on chromosome 12p11-q13.

Molecular Genetics

By whole-exome sequencing and/or direct sequencing of PCR products in affected members of 3 consanguineous Lebanese families with congenital ichthyosis mapping to chromosome 12q13-q14, Shigehara et al. (2016) identified homozygosity for 2 different missense mutations in the SDR9C7 gene, I200T (609769.0001) and R72W (609769.0002). The 2 families homozygous for the I200T mutation were from the same region in Lebanon and shared an identical haplotype around SDR9C7. Neither mutation was found in 300 population-matched controls.

In the male proband of a consanguineous Pakistani family with congenital ichthyosis, who was negative for mutation in known ARCI-associated genes, Karim et al. (2017) performed whole-exome sequencing and identified homozygosity for a 1-bp duplication in the SDR9C7 gene (609769.0003). His affected sisters were also homozygous for the duplication, which was not found in unaffected family members, in 100 controls, or in an in-house database of 20 exomes.