Prenatal case report and genetic analysis of Nance-Horan syndrome caused by a new NHS gene variation

doi:10.3969/j.issn.1673-8640.2026.02.005

Abstract

Abstract:

Objective To investigate the genetic cause of a fetus diagnosed with congenital cataract（CC） by prenatal ultrasound，and to analyze the pathogenic gene variations and prenatal ultrasound manifestations of Nance-Horan syndrome. Methods A sample of amniotic fluid from a pregnant woman at 24⁺³ weeks of gestation who was suspected of having bilateral CC in the fetus，as well as peripheral blood samples from the pregnant woman and her husband，were collected for family Trio-whole-exome sequencing（Trio-WES）. The candidate variations were verified by Sanger sequencing. The variations were analyzed by bioinformatics，and the distribution frequency of the variations was evaluated by searching public variation databases（dbSNP database，1000 Genomes database，ExAC database，gnomAD database and ESP database）. The literature reports of the variations were retrieved from disease-related databases（HGMD database，ClinVar database and OMIM database）. The pathogenicity of the variations was evaluated by protein prediction tools. Results The Trio-WES results showed that a hemizygous frameshift variation [NM_001291867.2：c.3799dup（p.Cys1267Leufs*18）] was present in the X chromosome of the fetus，and the pregnant woman was a heterozygous carrier of this variation，while her husband had the wild type. The c.3799dup（p.Cys1267Leufs*18） variation was not included in the public variation databases and disease-related databases，and it was a new variation. No other pathogenic variations were determined. Combined with the ultrasound characteristics of bilateral CC in the fetus，Nance-Horan syndrome caused by NHS gene variation was diagnosed. After genetic counseling，the pregnant woman chose to terminate the pregnancy. Conclusions Trio-WES can achieve precise molecular diagnosis of Nance-Horan syndrome in the fetal period. The c.3799dup（p.Cys1267Leufs*18） is a new variation of NHS gene，enriching the variation spectrum of this disease，and providing a reference for prenatal diagnosis and reproductive strategies.

Key words: NHS gene, Congenital cataract, Nance-Horan syndrome, Prenatal diagnosis, Whole-exome sequencing

CLC Number:

R446.7

ZHANG Man, TIAN Ruixia, SUN Zixiang, CHEN Cheng, WEI Zhuojun, ZHAO Xuliang. Prenatal case report and genetic analysis of Nance-Horan syndrome caused by a new NHS gene variation[J]. Laboratory Medicine, 2026, 41(2): 126-132.

Figures/Tables 4

References 46

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参考文献	发表时间	病例数	白内障	孕周	家族史	遗传原因	妊娠结局
本例胎儿		1	双侧	24	无	NHS基因变异（c.3799dup）	终止妊娠
GAARY等^[8]	1993年	1	双侧	18	有		终止妊娠
MONTEAGUDO等^[9]	1996年	3	2例双侧，1例单侧	15	有		终止妊娠
DRYSDALE等^[10]	1997年	1	双侧	19	有		出生
BURGESS等^[11]	1998年	1	双侧	18	无		出生
CENGIZ等^[12]	2001年	1	双侧	26	无		出生
LEHMAN等^[13]	2003年	1	单侧	28	无		出生
MASHIACH等^[14]	2004年	4	3例双侧，1例单侧	15	均有		1例终止妊娠
RECHES等^[15]	2007年	1	双侧	24	有	NHS基因变异（c.3908_3918del）	终止妊娠
LÉONARD等^[16]	2009年	1	双侧	27	无		出生
DASKALAKIS等^[17]	2010年	1	双侧	22	无		出生
LEE等^[18]	2013年	2	双侧	36	有		出生
CHEN等^[19]	2015年	1	双侧	22	无		终止妊娠
TRKOVA等^[20]	2016年	1	双侧	13	有	RAB3GAP1基因复合杂合变异（p.Glu180/p.Arg315）	出生
朱湘玉等^[21]	2017年	1	双侧		无	Xq25q26.1缺失引起的Lowe综合征	终止妊娠
AKSAY等^[22]	2020年	1	双侧	21	无	CRYBB1基因纯合变异（p.Lys252Arg）	终止妊娠
JUNG等^[23]	2021年	8	7例双侧，1例单侧	26	3例有		出生
QIN等^[24]	2022年	41	32例双侧，9例单侧	27	6例有	2 例非整倍体	31例终止妊娠
ZHENG等^[25]	2022年	1	双侧	24	无	OCRL基因变异（p.R334*）	终止妊娠
ROUXEL等^[26]	2022年	1	双侧	21	有	OCRL基因变异（p.Asp451Asn）	终止妊娠
TRAN等^[27]	2022年	1	双侧	22	有	NHS基因变异（c.107_109delCGCinsGG）	终止妊娠
ABDALLAH等^[28]	2023年	1	双侧	23	无	JAM3基因纯合变异（c.745dup）	出生
ITO等^[29]	2024年	1	双侧	25	有		出生
MAILLET等^[30]	2024年	5	均为双侧				1例终止妊娠
BURRILL等^[31]	2024年	1	单侧		有	OCRL基因变异（c.2582-1G>C）	终止妊娠

参考文献	发表时间	病例数	白内障	孕周	家族史	遗传原因	妊娠结局
本例胎儿		1	双侧	24	无	NHS基因变异（c.3799dup）	终止妊娠
GAARY等^[8]	1993年	1	双侧	18	有		终止妊娠
MONTEAGUDO等^[9]	1996年	3	2例双侧，1例单侧	15	有		终止妊娠
DRYSDALE等^[10]	1997年	1	双侧	19	有		出生
BURGESS等^[11]	1998年	1	双侧	18	无		出生
CENGIZ等^[12]	2001年	1	双侧	26	无		出生
LEHMAN等^[13]	2003年	1	单侧	28	无		出生
MASHIACH等^[14]	2004年	4	3例双侧，1例单侧	15	均有		1例终止妊娠
RECHES等^[15]	2007年	1	双侧	24	有	NHS基因变异（c.3908_3918del）	终止妊娠
LÉONARD等^[16]	2009年	1	双侧	27	无		出生
DASKALAKIS等^[17]	2010年	1	双侧	22	无		出生
LEE等^[18]	2013年	2	双侧	36	有		出生
CHEN等^[19]	2015年	1	双侧	22	无		终止妊娠
TRKOVA等^[20]	2016年	1	双侧	13	有	RAB3GAP1基因复合杂合变异（p.Glu180/p.Arg315）	出生
朱湘玉等^[21]	2017年	1	双侧		无	Xq25q26.1缺失引起的Lowe综合征	终止妊娠
AKSAY等^[22]	2020年	1	双侧	21	无	CRYBB1基因纯合变异（p.Lys252Arg）	终止妊娠
JUNG等^[23]	2021年	8	7例双侧，1例单侧	26	3例有		出生
QIN等^[24]	2022年	41	32例双侧，9例单侧	27	6例有	2 例非整倍体	31例终止妊娠
ZHENG等^[25]	2022年	1	双侧	24	无	OCRL基因变异（p.R334*）	终止妊娠
ROUXEL等^[26]	2022年	1	双侧	21	有	OCRL基因变异（p.Asp451Asn）	终止妊娠
TRAN等^[27]	2022年	1	双侧	22	有	NHS基因变异（c.107_109delCGCinsGG）	终止妊娠
ABDALLAH等^[28]	2023年	1	双侧	23	无	JAM3基因纯合变异（c.745dup）	出生
ITO等^[29]	2024年	1	双侧	25	有		出生
MAILLET等^[30]	2024年	5	均为双侧				1例终止妊娠
BURRILL等^[31]	2024年	1	单侧		有	OCRL基因变异（c.2582-1G>C）	终止妊娠