Basan综合征的临床特征、基因分析及文献回顾

刘周亮; 杨超; 汪慧君; 林志淼

doi:10.12376/j.issn.2097-0501.2023.02.006

Basan综合征的临床特征、基因分析及文献回顾

doi: 10.12376/j.issn.2097-0501.2023.02.006

南方医科大学皮肤病医院，广州 510091

基金项目:

国家自然科学基金面上项目 82073423

详细信息

通信作者:
林志淼，E-mail：zhimiaolin@bjmu.edu.cn

中图分类号: R758.59
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出版历程
- 收稿日期: 2023-02-16
- 录用日期: 2023-03-10
- 网络出版日期: 2023-05-05

Clinical Features and Mutation Analysis of the SMARCAD1 Gene in a Family with Basan Syndrome and a Literature Review

Dermatology Hospital, Southern Medical University, Guangzhou 510091, China

Funding:

General Program of the National Natural Science Foundation of China 82073423

More Information

Corresponding author: LIN Zhimiao, E-mail: zhimiaolin@bjmu.edu.cn

摘要

摘要: 目的总结Basan综合征的临床特征及基因分析。方法对2022年于南方医科大学皮肤病医院收治并确诊的Basan综合征家系，归纳一般资料，总结临床特征及基因型特点，并回顾性分析既往报道所有Basan综合征患者的特点及相关基因突变。结果共收集确诊Basan综合征患者18例，其中男性9例，女性9例。18例均出现出生时即无指纹(18/18，100%)，部分患者出现指关节垫、掌跖角化过度、甲萎缩、甲分离、甲纵脊等。症状轻重不一。同时发现7例患者SMARCAD1 (NM_020159.5)基因1号内含子上出现c.-10+1G＞T(即c.378+1G＞T)突变，造成异常剪接。结论本文可为疾病的早期诊断提供帮助，有助于提高临床医生的诊断与鉴别水平。
- Basan综合征 /
- SMARCAD1基因 /
- 无皮纹病 /
- 剪接突变
Abstract: Objective To summarize the clinical features of a family with Basan syndrome and to analyze mutation of the SMARCAD1 gene. Methods The Basan family was diagnosed at Dermatology Hospital, Southern Medical University in 2022. Backgroud data was collected, and clinical and genetic characteristics were analyzed. Meanwhile, a retrospective analysis of features and associated genetic mutations reported in all patients with Basan syndrome was conducted. Results A total of 18 patients with Basan syndrome were identified, including 9 males and 9 females. All 18 patients had no fingerprints at birth (18/18, 100%), and some patients had knuckle pads, palmoplantar hyperkeratosis, nail atrophy, nail separation, and longitudinal nail ridges. Symptoms vary in severity. At the same time, it was found that c.-10+1G > T (as well as c.378+1G > T)mutations appeared on the intron 1 of the SMARCAD1 (NM_020159.5) gene in 7 patients, resulting in abnormal splicing. Conclusions This article provides help for the early diagnosis of Basan syndrome and helps to improve the diagnosis and differentiation level of clinicians.
- Basan syndrome /
- SMARCAD1 gene /
- adermatoglyphia /
- splicing mutation
注释:

作者贡献：刘周亮负责资料汇总和论文撰写；林志淼、杨超负责临床资料收集、数据分析；林志淼、汪慧君指导研究设计；林志淼、汪慧君、刘周亮修改论文。

利益冲突：所有作者均声明不存在利益冲突。

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图 1 Basan综合征(BSN)患者家系图

Figure 1. Pedigree of the Basan sydrome(BSN) family

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图 2 BSN患者临床表现

A.双手掌呈对称网状、异色样改变、无指纹；B.指甲可见甲纵脊；C.足底皮肤异色样改变、角化过度、无趾纹；D.足跟角化过度；E.趾甲分离，可见甲纵脊

Figure 2. Clinical manifestations of a BSN patient

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图 3 先证者及家庭成员Ⅳ-8的Sanger测序结果

A.先证者SMARCAD1基因存在杂合突变c.-10+1G＞T(即c.378+1G＞T)，箭头示突变位点；B.箭头示Ⅳ-8未见该突变

Figure 3. Sanger sequencing results of the pathogenic mutant gene of the proband, Ⅳ-8

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图 4 ADG、BSN、HRZ临床表现韦恩图

Figure 4. Veen diagram on clinical manifestations between ADG, BSN and HRZ

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表 1 BSN临床特征及基因突变情况统计分析

Table 1. Clinical features and mutations with BSN

表型或基因型	Baird^[8](1964)N=13	Basan^[9](1965)N=8		Reed等^[10] (1983)N=4		Limova等^[11](1993)N=3	Gagey-Caron等^[12](2009)N=3
无皮纹病	13/13	6/8		4/4		3/3	3/3
少汗症	13/13	2/8		4/4		3/3	3/3
肢端大疱	/	0/8		2/4		3/3	2/3
先天性粟丘疹	13/13	/		2/4		0/3	2/3
指(趾)挛缩	7/13	1/8		0/4		3/3	0/3
角化过度	1/13(1例活检)	2/8		/		1/3(1例活检)	1/3
甲损害	-	甲纵脊(3/8)		甲萎缩(1/4)		/	0/3
通贯手	-	/		3/4		/	0/3
其他特征	对天气冷暖敏感、双侧脚趾形成蹼(5/13)	并指(5/8)、点状疣(3/8)、杵状指(3/8)		更加耐热(3/4)、肢端更易降温(3/4)、锥形指尖(1/4)		抓持困难3/3、锥形指尖1/3、	手足曾起疱的部位出现色素减退斑块
SMARCAD1突变	/	/		/		/	/

表型或基因型	Luna等^[13](2012)N=5	Marks等^[6](2014)和Adra等^[14](2000)N=7		Li等^[1](2016)N=8		Chang等^[3](2018)N1=2、N2=4
无皮纹病	5/5	7/7		8/8		2/2	3/4
少汗症	0/5	2/7		8/8		/	/
肢端大疱	1/5	4/7		8/8		1/2	4/4
先天性粟丘疹	2/5	7/7		8/8		1/2	4/4
指趾挛缩	/	/		8/8		1/2	3/4
角化过度	1/5(1例活检)	/		2/8		/	/
甲损害	1/5	/		甲萎缩(1/8)		/	/
通贯手	/	/		1/8		/	/
其他特征	双侧指(趾)并指畸形3/5	/		色素沉着斑5/8、指关节垫7/8		双侧并趾畸形1/2，第五指斜指	第五指斜指
SMARCAD1突变	/	c.-10+3A＞T (即c.378+3A＞T)		c.-10+1G＞T (即c.378+1G＞T)		116 kb缺失	c.-10+5G＞A (即c.378+5G＞A)

表型或基因型	Valentin等^[4](2018)N=1	Elhaji等^[7](2021)N1=12、N2=3		Nieto等^[5](2021)N1=1、N2=1		Xiong等^[2](2022)N=12	本家系N=18
无皮纹病	1/1	12/12	3/3	+	+	0	+
少汗症	/	12/12	3/3	/	/	+	+
肢端大疱	1/1	12/12	0/3	+	+	+	/
先天性粟丘疹	1/1	12/12	3/3	+	+	+	/
指(趾)挛缩	/	0/12	0/3	/	/	+	+
角化过度	1/1	0/12	3/3	/	/	+	/
甲损害	脆甲(1/1)	0/12	甲纵脊(3/3)、甲Beau线(3/3)	/	甲营养不良	甲纵脊(+)	甲分离、甲纵脊
通贯手	/	0/12	0/3	/	/	/	-
其他特征	色素沉着斑1/1	易中暑12/12、蹼状指4/12；	锥形指尖3/3；关节垫2/3、1/3出现杵状指	毛发稀疏、先天性幽门狭窄、双侧五指短指，有家族史	有家族史	锥形指尖(+)、4例死于鳞状细胞癌的转移	指关节垫、掌跖异色样改变
SMARCAD1突变	c.-10+2T＞G (即c.378+2T＞G)	复杂性重排	c.-16_-10+7del(即c.372_378+7del)	c.-10+1G＞A (即c.378+1G＞A)	/	c.-10+5G＞A (即c.378+5G＞A)	c.-10+1G＞T (即c.378+1G＞T)
N表示患者数量，+表示阳性，-表示阴性，/表示未知

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表 2 SMARCAD1基因突变的既往报道

Table 2. SMARCAD1 mutations described in previous literature

疾病类型	基因突变	参考文献
ADG	c.-10+1G＞T(即c.378+1G＞T)	[15]
	c.-10+2T＞C(即c.378+2T＞C)，c.-10 + 5G＞C (即c.378+5G＞C)，c.-10 + 1G＞A(即c.378+1G＞A)	[17]
	c.-10+1G＞T(即c.378+1G＞T)	[18]
BSN	c.-10+3A＞T(即c.378+3A＞T)	[6]
	116 kb heterozygous deletion	[3]
	c.-10+2T＞G(即c.378+2T＞G)	[2]
	c.-10+1G＞A(即c.378+1G＞A)	[5]
	c.-10+5G＞A(即c.378+5G＞A)	[2]
	c.-16_-10+7del(即c.372_378+7del)，复杂的结构性重排，包括约50.9 kb的缺失(chr4:94, 203365-94, 254, 728)和约23.4 kb的重复(chr4:94, 175, 790-94)	[7]
HRZ	c.-10+2T＞C(即c.378+2T＞C), c.-10+2_3insT(即c.378+2_3insT), c.-25 _-10+2del(即c.363_378+2del)	[21]
	g.9452297-94253585del	[22]
	c.-10_-10+11del(即c.378_378+11del), c.-10+2delT(即c.378+2delT), c.-25_-10+2del(即372_378+2del)	[19]
ADG：无皮纹病；BSN：Basan综合征；HRZ：Huriez综合征

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参考文献(22)

[1]	Li M, Wang J, Li Z, et al. Genome-wide linkage analysis and whole-genome sequencing identify a recurrent SMARCAD1 variant in a unique Chinese family with Basan syndrome[J]. Eur J Hum Genet, 2016, 24(9): 1367-1370. doi: 10.1038/ejhg.2016.15
[2]	Xiong Y, Chen T, Yu J, et al. Association between mutation in SMARCAD1 and Basan syndrome with cutaneous squamous cell carcinoma[J]. Dis Markers, 2022, 2022: 7840710.
[3]	Chang X, Li D, Tian L, et al. Heterozygous deletion impacting SMARCAD1 in the original kindred with absent dermatoglyphs and associated features (Baird, 1964)[J]. J Pediatr, 2018, 194: 248-252. e2. doi: 10.1016/j.jpeds.2017.11.011
[4]	Valentin MN, Solomon BD, Richard G, et al. Basan gets a new fingerprint: mutations in the skin-specific isoform of SMARCAD1 cause ectodermal dysplasia syndromes with adermatoglyphia[J]. Am J Med Genet A, 2018, 176(11): 2451-2455. doi: 10.1002/ajmg.a.40485
[5]	Nieto Benito LM, Molina López I, Feito Rodríguez M, et al. Ectodermal dysplasia with congenital adermatoglyphia (Basan syndrome): report of two cases presenting with extensive congenital milia[J]. Pediatr Dermatolo, 2021, 38(2): 530-532. doi: 10.1111/pde.14512
[6]	Marks KC, Banks WR, Cunningham D, et al. Analysis of two candidate genes for Basan syndrome[J]. Am J Med Genet A, 2014, 164A(5): 1188-1191.
[7]	Elhaji Y, van Henten TMA, Ruivenkamp CAL, et al. Two SMARCAD1 variants causing Basan syndrome in a Canadian and a Dutch family[J]. JID Innov, 2021, 1(3): 100022. doi: 10.1016/j.xjidi.2021.100022
[8]	Baird HR. Kindred showing congenital absence of the dermal ridges (fingerprints) and associated anomalies[J]. J Pediatr, 1964, 64: 621-631. doi: 10.1016/S0022-3476(64)80610-7
[9]	Basan M. Ectodermal dysplasia. Missing papillary pattern, nail disorders and furrows on 4 fingers[J]. Arch Klin Exp Dermatol, 1965, 222(6): 546-557. doi: 10.1007/BF00514755
[10]	Reed T, Schreiner RL. Absence of dermal ridge patterns: genetic heterogeneity[J]. Am J Med Genet, 1983, 16(1): 81-88. doi: 10.1002/ajmg.1320160113
[11]	Limova M, Blacker KL, Leboit PE. Congenital absence of dermatoglyphs[J]. J Am Acad Dermatol, 1993, 29(2 Pt 2): 355-358.
[12]	Gagey-Caron V, Stalder JF, Barbarot S. Basan's syndrome: congenital absence of dermatoglyphs and milia[J]. Ann Dermatol Venereol, 2009, 136(5): 419-421. doi: 10.1016/j.annder.2008.09.018
[13]	Luna PC, Larralde M. Profuse congenital familial milia with absent dermatoglyphics (Basan's syndrome): description of a new family[J]. Pediatr Dermatol, 2012, 4(29): 527-529.
[14]	Adra CN, Donato J, Badovinac R, et al. SMARCAD1, a novel human helicase family-defining member associated with genetic instability: cloning, expression, and mapping to 4q22-q23, a band rich in breakpoints and deletion mutants involved in several human diseases[J]. Genomics, 2000, 69(2): 162-173. doi: 10.1006/geno.2000.6281
[15]	Nousbeck J, Burger B, Fuchs-Telem D, et al. A mutation in a skin-specific isoform of SMARCAD1 causes autosomal-dominant adermatoglyphia[J]. Am J Hum Genet, 2011, 89(2): 302-307. doi: 10.1016/j.ajhg.2011.07.004
[16]	Burger B, Fuchs D, Sprecher E, et al. The immigration delay disease: adermatoglyphia-inherited absence of epider-mal ridges[J]. J Am Acad Dermatol, 2011, 64(5): 974-980. doi: 10.1016/j.jaad.2009.11.013
[17]	Nousbeck J, Sarig O, Magal L, et al. Mutations in SMARCAD1 cause autosomal dominant adermatoglyphia and perturb the expression of epidermal differentiation-associated genes[J]. Br J Dermatol, 2014, 171(6): 1521-1524. doi: 10.1111/bjd.13176
[18]	Alruwaili J, Hai A. Adermatoglyphia[J]. Natl Med J India, 2019, 32(4): 253. doi: 10.4103/0970-258X.291296
[19]	Loh AYT, Apoljar S, Neo GYW, et al. Huriez syndrome: additional pathogenic variants supporting allelism to SMARCAD syndrome[J]. Am J Med Genet A, 2022, 188(6): 1752-1760. doi: 10.1002/ajmg.a.62703
[20]	Mukherjee S, Maurya MK, Kumar P. Clinical images: Huriez syndrome, a rare scleroderma mimic[J]. Arthritis Rheumatol, 2022, 74(10): 1675. doi: 10.1002/art.42242
[21]	Gunther C, Lee-Kirsch MA, Eckhard J, et al. SMARCAD1 haploinsufficiency underlies Huriez syndrome and associated skin cancer susceptibility[J]. J Invest Dermatol, 2018, 138(6): 1428-1431. doi: 10.1016/j.jid.2018.01.015
[22]	Loh A, Ho CM, Muthiah S, et al. Huriez syndrome caused by a large deletion that abrogates the skin-specific isoform of SMARCAD1[J]. Br J Dermatol, 2021, 184(6): 1205-1207. doi: 10.1111/bjd.19799