PMID- 34620209 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211011 IS - 1755-8166 (Print) IS - 1755-8166 (Electronic) IS - 1755-8166 (Linking) VI - 14 IP - 1 DP - 2021 Oct 7 TI - Allelic and dosage effects of NHS in X-linked cataract and Nance-Horan syndrome: a family study and literature review. PG - 48 LID - 10.1186/s13039-021-00566-x [doi] LID - 48 AB - 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. CI - (c) 2021. The Author(s). FAU - Miller, Caroline AU - Miller C AD - Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 608, Rochester, NY, 14642, USA. FAU - Gertsen, Benjamin G AU - Gertsen BG AD - Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 608, Rochester, NY, 14642, USA. FAU - Schroeder, Audrey L AU - Schroeder AL AD - Division of Medical Genetics, University of Rochester Medical Center, Rochester, NY, 14642, USA. FAU - Fong, Chin-To AU - Fong CT AD - Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, 14642, USA. AD - Department of Medicine, University of Rochester Medical Center, Rochester, NY, 14642, USA. FAU - Iqbal, M Anwar AU - Iqbal MA AUID- ORCID: 0000-0002-7552-1703 AD - Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 608, Rochester, NY, 14642, USA. anwar_iqbal@urmc.rochester.edu. FAU - Zhang, Bin AU - Zhang B AUID- ORCID: 0000-0002-1671-402X AD - Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 608, Rochester, NY, 14642, USA. bin_zhang@urmc.rochester.edu. AD - Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, 14642, USA. bin_zhang@urmc.rochester.edu. AD - Department of Pathology and Pediatrics, University of Rochester Medical Center, 601 Elmwood Ave, Box 608, Rochester, NY, 14642, USA. bin_zhang@urmc.rochester.edu. LA - eng PT - Journal Article DEP - 20211007 PL - England TA - Mol Cytogenet JT - Molecular cytogenetics JID - 101317942 PMC - PMC8496034 OTO - NOTNLM OT - Allelic disorders OT - Array-comparative genomic hybridization (aCGH) OT - Dosage effect OT - FISH OT - Gene disruption OT - Karyotyping OT - NHS OT - Nance-Horan syndrome OT - X chromosome inactivation (XCI) OT - X-autosome translocation OT - X-linked cataract COIS- The authors have declared that no conflict of interest exists. EDAT- 2021/10/09 06:00 MHDA- 2021/10/09 06:01 PMCR- 2021/10/07 CRDT- 2021/10/08 05:44 PHST- 2021/02/27 00:00 [received] PHST- 2021/06/08 00:00 [accepted] PHST- 2021/10/08 05:44 [entrez] PHST- 2021/10/09 06:00 [pubmed] PHST- 2021/10/09 06:01 [medline] PHST- 2021/10/07 00:00 [pmc-release] AID - 10.1186/s13039-021-00566-x [pii] AID - 566 [pii] AID - 10.1186/s13039-021-00566-x [doi] PST - epublish SO - Mol Cytogenet. 2021 Oct 7;14(1):48. doi: 10.1186/s13039-021-00566-x.