Identification of a microdeletion at Xp22.13 in a Taiwanese family presenting with Nance-Horan syndrome

Abstract

,9,10 Nance-Horan syndrome (NHS) is a rare X-linked disorder characterized by congenital cataracts, dental anomalies and mental retardation. The disease has been linked to a novel gene termed NHS located at Xp22.13. The majority of pathogenic mutations of the disease include nonsense mutations and small deletions and insertions that lead to truncation of the NHS protein. In this study, we identified a microdeletion of B0.92 Mb at Xp22.13 detected by array-based comparative genomic hybridization in two brothers presenting congenital cataract, dental anomalies, facial dysmorphisms and mental retardation. The deleted region encompasses the REPS2, NHS, SCML1 and RAI2 genes, and was transmitted from their carrier mother who presented only mild cataract. Our findings are in line with several recent case reports to indicate that genomic rearrangement involving the NHS gene is an important genetic etiology underlying NHS.

Nance–Horan syndrome—The oral perspective on a rare disease

“…The absence of the other genes than NHS may have affected the clinical symptoms and health conditions of the affected brothers. Especially, the absence of the retinoic‐acid‐induced protein 2 ( RAI2 ) may have contributed to the bone abnormalities and the mental retardation in the affected brothers [Liao et al, ]. In addition, we cannot exclude the possibility that the absence of the other eight genes may have an additive effect on the tooth morphology in these two brothers.…”

“…The syndrome is characterized by congenital bilateral cataract, dental abnormalities, dysmorphic traits like anteverted pinnae, short fingers, and a broad nose [Ding et al, ; Tug et al, ; Li et al, ]. Furthermore, the literature includes descriptions of mental retardation and autism in NHS, but these findings are more inconsistent [Toutain et al, ; Liao et al, ]. The majority of the studies published focus on the congenital cataract and/or the genetic mutations and with a limited description of oral findings [Florijn et al, ; Huang et al, ; Reches et al, ].…”

A novel Xp22.13 microdeletion in Nance‐Horan syndrome

“…Overall, only a few patients with tetralogy of Fallot have been described (Van Esch et al, ; Mathys et al, ; Coccia et al, ). Finally, Liao et al () described two Taiwanese brothers with Nance‐Horan syndrome carrying a microdeletion at Xp22.13. Similar to our patients, they presented with hypotonia and global developmental delay, in addition to the typical NHS phenotype.…”

“…The observation of a significant variability in terms of intellectual disability has suggested a possible modulation effect of other genes. A potential role of the flanking genes has previously been discussed in patients carrying a microdeletion at Xp22.13 (Liao et al, ).…”

Nance-Horan Syndrome

“…The dental abnormalities include dental agenesis, supernumerary teeth, impacted teeth, unusually wide spaces between some of the teeth (diastena) (3). The incisors may be tapered and screw driven shaped, almost like Hutchinson's teeth as seen in congenital syphilis.…”