Clinical features and genetic analysis of two Chinese families with X-linked ichthyosis

Abstract

Objective: Recessive X-linked ichthyosis (RXLI) caused by deficiency of the steroid sulfatase gene (STS) has a reported prevalence of 1/2000 to 1/6000. The present study aimed to characterize the phenotypes and genotypes of two Chinese families with RXLI.

Methods: The patients were referred to the Family Planning Research Institute of Hunan Province for genetic counseling. Their skin phenotypes were photographed, and venous blood was drawn and used for chromosomal microarray analysis (CMA).

Results: The skin phenotype of the proband from the first family was characterized by generalized skin dryness and scaling, with noticeable dark brown, polygonal scales on his trunk and extensor surfaces of his extremities. The proband from the second family had an atypical phenotype showing mild skin dryness over his entire body, slight scaling on his abdomen, and small skin fissures on his arms and legs. No mental disability or developmental anomaly was noted in either proband. CMA revealed that both probands carried a 1.4-Mb deletion on chromosome Xp22.31 involving four Online Mendelian Inheritance in Man-listed genes including STS.

Conclusions: Our findings add knowledge to the genotype and phenotype spectrum of RXLI, which may be helpful in genetic counseling and prenatal diagnosis.

Keywords: X-linked ichthyosis; chromosomal microarray; genetic counselling; phenotype variability; scaling; skin fissures; steroid sulfatase.

Figure 1.

Pedigrees of the two Chinese families with RXLI. Squares and circles indicate males and females, respectively. Squares filled with black represent affected males. Circles filled with grey show the female carriers of pathogenic mutations based on recessive inheritance, and a question mark notes the uncertainty regarding a carrier. A symbol with a diagonal line represents a deceased individual. The proband in each family is shown by an arrow.

Figure 2.

The skin phenotype of the 28-year-old proband in family 1. The proband presented with generalized skin dryness and scaling (a). Dark brown and polygonal scales were visible on his abdomen (b) and the extensor surfaces of his arms (c) and legs (d).

Figure 3.

The skin phenotype of the 37-year-old proband in family 2. The proband showed mild skin dryness over the entire body, slight scaling on his abdomen (a), and small skin fissures on his arms (b) and legs (c).

Figure 4.

CMA identified segment losses within region Xp22.31 in the probands. Sample S1 and S1U represent the 28-year-old proband and his maternal uncle (II-3), respectively, in family 1. Samples S2, S2M, and S2F correspond to the 37-year-old proband, his mother, and father, respectively, in family 2.