Left‐sided CHILD syndrome caused by a nonsense mutation in the NSDHL gene

Abstract

Congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome is a rare X-linked dominant malformation syndrome characterized by unilaterally distributed ichthyosiform nevi, often sharply delimited at the midline, and ipsilateral limb defects. At least two-thirds of cases demonstrate involvement of the right side. Mutations in an essential enzyme of cholesterol biosynthesis, NAD(P)H steroid dehydrogenase-like [NSDHL], have been reported in five unrelated patients with right-sided CHILD syndrome and in a sixth patient with bilaterally, symmetric nevi and mild skeletal anomalies, but not with CHILD syndrome as originally defined. Although all of the molecularly diagnosed cases with the CHILD phenotype to date have had right-sided disease, we report here a novel nonsense mutation (E151X) of NSDHL in an infant with left-sided CHILD syndrome. This result demonstrates that both right- and left-sided CHILD syndrome can be caused by mutations in the same gene.

Malformation syndromes caused by disorders of cholesterol synthesis

“…Alopecia may occur, usually on the more involved side, and nails are often dystrophic. Involvement of the right side of the body is more common than the left, although visceral involvement occurs more frequently in left-sided cases ( 258,263 ).…”

“…Although CHILD Syndrome results from a cholesterol biosynthetic enzyme defi ciency, cholesterol levels in plasma from affected females are normal, and abnormal metabolites may be diffi cult to detect ( 263 ). Indeed, in Nsdhl deficient female mice, plasma sterol profi les are normal.…”

“…Three of 23 (13%) patients reported by Bornholdt et al ( 258 ) had unilateral renal agenesis. Lung hypoplasia, with a small chest wall leading to respiratory distress, has also been reported ( 263,268 ).…”

A Novel Somatic Mutation of the 3β-Hydroxysteroid Dehydrogenase Gene in Sporadic Cutaneous Verruciform Xanthoma

“…Hummel et al 10 reported nonsense mutation E151X on exon 5, and Murata et al 11 have reported another mutation, Y349C on exon 8 of the NSDHL gene. Although none of the reported exon 4 and 6 mutations are detected in our VX cases, the occurrence of a mutation in the NSDHL gene, along with morphological similarities in the skin lesions of CHILD syndrome and VX, supports the functional role of this gene in the pathogenesis of VX.…”

“…1,10,11,17,18 Evaluation for HPV in VX has been studied and has included types 6, 7, 11, 12, 16 to 19, 31, 33, 35, 37, 44 to 47, 53, 54, and 58. 6,13,[21][22][23] While most studies failed to show evidence of HPV, 1 study 13 demonstrated by immunohistochemical analysis a positive reaction in the upper epidermal keratinocytes, which was confirmed by electron microscopy and by PCR, which also detected HPV-DNA 6a.…”