Nance–Horan syndrome in females due to a balanced X;1 translocation that disrupts the <i>NHS</i> gene: Familial case report and review of the literature

Gómez-Laguna, Laura; Martínez-Herrera, Alejandro; Rosa, Alejandra Del Pilar Reyes-de la; García-Delgado, Constanza; Nieto-Martínez, Karem; Fernández-Ramírez, Fernando; Valderrama-Atayupanqui, Tania Yanet; Morales-Jiménez, Ariadna Berenice; Villa-Morales, Judith; Kofman, Susana; Cervantes, Alicia; Morán-Barroso, Verónica Fabiola

doi:10.1080/13816810.2017.1363245

Cited by 10 publications

(11 citation statements)

References 31 publications

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“…Previous studies illustrated that variations in the NHS gene could induce X-linked cataracts and NHS [10–12]. However, the identical association between the genotype and phenotype was unclear.…”

Section: Discussionmentioning

confidence: 99%

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Whole exome sequencing identified a novel truncation mutation in the NHS gene associated with Nance-Horan syndrome

et al. 2019

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BackgroundNance-Horan syndrome (NHS) is an X-linked inheritance disorder characterized by bilateral congenital cataracts, and facial and dental dysmorphism. This disorder is caused by mutations in the NHS gene. However, NHS may be difficult to detect in individuals with subtle facial dysmorphism and dental abnormalities in whom congenital cataracts are the primary clinical manifestations.MethodsIn this study, we present a three-generation family with NHS. Whole exome sequencing was performed to determine the potential pathogenic variant in the proband. Further validation was explored with Sanger sequencing in 9 of the available individuals of the family and additional 200 controls.ResultsA novel truncation mutation in gene NHS (c.C4449G, p.Tyr1483Ter) was found in the proband, who presented with a long-narrow face, prominent nose and large anteverted pinnae ear, screw-driver like incisors, mild mulberry like molars, one missing maxillary second molar and malocclusion. We found this mutation was detected in 2 male patients and 4 female carriers in the family. However, the mutation was never detected in the control subjects.ConclusionsIn conclusion, we identified a novel truncation mutation in the NHS gene, which might associate with NHS. Our review on the NHS studies illustrated that NHS has significantly clinical heterogeneity. And NHS mutations in the NHS-affected individuals typically result in premature truncation of the protein. And the new mutation revealed in this study would highlight the understanding of the causative mutations of NHS.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0725-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…The mother had a preferential inactivation of the normal X chromosome and no mRNA isoform of NHS was detected. This study implied that NHS could be due to the disruption of NHS gene expression [12].…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing identified a novel truncation mutation in the NHS gene associated with Nance-Horan syndrome

et al. 2019

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“…A review of the literature revealed an additional report of NHS disruption due to a translocation. In this case, disruption was caused by a balanced (X;1) translocation [ 21 ]. As with our report, the patients examined in this study were female.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, a preferential inactivation of the normal X chromosome has been reported to cause X-linked disorders in the female carriers of an X-autosome translocation carriers [ 23 – 25 ]. It appears to occur in individuals with a balanced X-autosome translocation disrupting the NHS gene, and cause a phenotype consistent with NHS, in particular the facial characteristics and cataracts [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…NHS is most commonly due to nonsense mutations and small deletions [ 21 , 28 ] and only one missense mutation has been reported [ 29 ]. NHS transcriptional alteration, likely reduction due to complex gene rearrangements and/or intronic enhancer deletions, may cause X-linked cataract, an allelic disorder without other features such as dental anomalies, dysmorphism, and developmental delay [ 6 ] (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Allelic and dosage effects of NHS in X-linked cataract and Nance–Horan syndrome: a family study and literature review

et al. 2021

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Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder caused by mutation in the NHS gene on chromosome Xp22.13. (OMIM 302350). Classic NHS manifested in males is characterized by congenital cataracts, dental anomalies, dysmorphic facial features and occasionally intellectual disability. Females typically have a milder presentation. The majority of reported cases of NHS are the result of nonsense mutations and small deletions. Isolated X-linked congenital cataract is caused by non-recurrent rearrangement-associated aberrant NHS transcription. Classic NHS in females associated with gene disruption by balanced X-autosome translocation has been infrequently reported. We present a familial NHS associated with translocation t(X;19) (Xp22.13;q13.1). The proband, a 28-year-old female, presented with intellectual disability, dysmorphic features, short stature, primary amenorrhea, cleft palate, and horseshoe kidney, but no NHS phenotype. A karyotype and chromosome microarray analysis (CMA) revealed partial monosomy Xp/partial trisomy 19q with the breakpoint at Xp22.13 disrupting the NHS gene. Family history revealed congenital cataracts and glaucoma in the patient’s mother, and congenital cataracts in maternal half-sister and maternal grandmother. The same balanced translocation t(X;19) was subsequently identified in both the mother and maternal half-sister, and further clinical evaluation of the maternal half-sister made a diagnosis of NHS. This study describes the clinical implication of NHS gene disruption due to balanced X-autosome translocations as a unique mechanism causing Nance–Horan syndrome, refines dose effects of NHS on disease presentation and phenotype expressivity, and justifies consideration of karyotype and fluorescence in situ hybridization (FISH) analysis for female patients with familial NHS if single-gene analysis of NHS is negative.

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Cornea and Sclera

Yanoff,

Sassani

2025

Ocular Pathology

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Nance–Horan syndrome in females due to a balanced X;1 translocation that disrupts the NHS gene: Familial case report and review of the literature

Cited by 10 publications

References 31 publications

Whole exome sequencing identified a novel truncation mutation in the NHS gene associated with Nance-Horan syndrome

Whole exome sequencing identified a novel truncation mutation in the NHS gene associated with Nance-Horan syndrome

Allelic and dosage effects of NHS in X-linked cataract and Nance–Horan syndrome: a family study and literature review

Cornea and Sclera

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