Genetic analysis of a 12-year-old boy with X-linked ichthyosis in association with sclerosing glomerulonephritis

Abstract

Abstract. In this study, we report the case of a 12-year-old male with X-linked ichthyosis (XLI) in association with glomerular sclerosis, and our investigation into the deletion pattern of the STS gene and the flanking regions in DNA samples of family members. We observed no features typical of renal osteodystrophy or rickets, with the exception of short stature, in the three afffected male family members. Audiometry, visual acuity and olfactory sensation were normal. By performing PCR analysis of the steroid sulfatase (STS) gene and flanking regions on our patients, we discovered a complete deletion that involved the entire region from DXS1139 to DXF22S1. Further studies are required to determine whether the STS gene or the co-deleted flanking sequences are the cause of renal disease associated with XLI. IntroductionX-linked ichthyosis (XLI; OMIM #308100) is an inherited metabolic disorder resulting from a steroid sulfatase (STS) deficiency (1). It affects ~1:2,000-6,000 males, with little racial or geographic variation (2-4). Of the males affected, >90% manifest with generalized exfoliation of the skin within a few weeks of being born. Later, they develop large, polygonal, dark-brown scales symmetrically distributed over the extremities, trunk and neck, but typically sparing the face, palms and soles. The skin lesions persist throughout the life of the patient. Extracutaneous manifestations are common, particularly with corneal opacities and cryptorchidism (4). Other associated features, although extremely rare, include mental retardation, epilepsy, pyloric hypertrophy, congenital defects of the abdominal wall and acute lymphoblastic leukemia (3,5).For the majority of affected males (90%), XLI is caused by a STS deficiency due to the complete deletion of the STS gene located on the short arm of the X chromosome (Xp22.3). The remaining 10% of males demonstrate a point mutation or partial deletion (4,6,7). Larger deletions involving neighboring genes (contiguous gene deletion syndromes) may result in XLI associated with Kallman syndrome (KS) or X-linked recessive chondrodysplasia punctata (CDXP) (4,6,7).In this study, we report on the case of a 12-year-old male with XLI in association with glomerular sclerosis. Ichthyosis also affects two other members of the patient's family. The case report describes our investigation into the deletion pattern of the STS gene and flanking regions in DNA samples of the family members. The study was approved by the Ethics Committee of The Second Xiangya Hospital of Central South University, Changsha, Hunan, China and consent was obtained from the the patient's family Case reportPatient history. A 12-year-old male presented with increasing nocturnal urine volume for five years, pallor for one year and discontinuous tetany for the previous two days. At seven years old, the increase in urine volume, ~800 ml/night, in addition to enuresis were noted, but aggravated gradually. There was no history of oliguria or edema. The patient was the product of a non-consanguineous marriage and...

X‐linked ichthyosis: Molecular findings in four pedigrees with inconspicuous clinical manifestations

“…Puri and colleagues reported a 3‐year‐old Caucasian male XLI baby with deletions of four OMIM genes including HDHD1 , STS , VCX, and PNPLA4 , and this child had manifestations of skin dryness in the limbs with adherent scales, complicated by pyloric stenosis, epilepsy, polymicrogyria, thin hair, poor dentition, retinitis pigmentosa, malformation of cortical development, and developmental delay. Song and colleagues reported a 12‐year‐old male XLI patient with deletions of HDHD1 , STS , VCX, and PNPLA4 genes, and the child had large, thick, dark brown, and polygonal scales, complicated by glomerular sclerosis and microsomia. In addition, Hand and colleagues reported three males with XLI in whom four OMIM genes ( HDHD1 , STS , VCX, and PNPLA ) were deleted, and these patients had only invisible scales adherent to the skin, or dryness or eczema, complicating by other clinical manifestations, such as autism, microsomia, neurofibroma, and developmental delay.…”

Multiple Bony Deformities and Short Stature in a Child with Lamellar Ichthyosis, What more can we do? A Case Report

“…Deletions of 12q13 coding for keratin 1 can involve12q13-14 coding for Vitamin D receptor causing a cellular Vitamin D resistance [ 8 ]. Similarly, deletion around Xp22.31 coding for steroid sulfatase can involve Xp22.1 coding for Phosphate Endopeptidase Homolog X- linked leading to hypophosphatemic rickets which is also Vitamin D resistant [ 9 ].…”

Steroid sulfatase deficiency causes cellular senescence and abnormal differentiation by inducing Yippee-like 3 expression in human keratinocytes

“…Therefore, further study is needed to determine the association between STAT5a and YPEL3 expression, and the relationship between factors affecting ERα stability and STS. Currently, XLI studies have been conducted mainly using samples from patients [43][44][45] .…”