Advances in studies on genetics of syndromes combining sensorineural hearing loss with scoliosis
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Abstract: Sensorineural hearing loss and scoliosis are common in several disease groups, such as hereditary connective tissue syndrome, hereditary motor and sensory neuropathy, lysosomal storage syndrome and endocrine disorders.These diseases have significant phenotypic diversity and genetic heterogeneity, different subtypes show inconsistent characteristics of deafness.Moreover, subtypes with similar clinical manifestations have different genetic mechanisms.Using new generation sequencing technology, considerable progress has been achieved in these diseases.This paper reviews clinical manifestations and genetic mechanism of syndromes combining sensorineural hearing loss and scoliosis.
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Key words:
- scoliosis /
- sensorineural hearing loss /
- syndromic deafness /
- genetics
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表 1 脊柱侧凸合并SNHL相关综合征的临床特点及致病基因
综合征亚型名称 基因 遗传模式 听力损失
发病年龄听力损失程度 听力损失
类型听力图
曲线STL1 COL2A1 常显 儿童期 轻度到中度 SNHL/传导性聋/混合性聋 下降型 成骨不全症 COL1A1/COL1A2 常显 20~40岁 未提及 SNHL/传导性聋/混合性聋 未提及 Steel综合征 COL27A1 常隐 儿童期 极重度 SNHL 未提及 Ehlers-Danlos综合征脊柱侧凸2型 FKBP14 常隐 儿童期 重度 SNHL 下降型 EDS Kosho型/EDS肌肉挛缩型 CHST14 常隐 未提及 未提及 SNHL 未提及 EDS 4B型 ZNF469 常隐 未提及 未提及 SNHL/传导性聋/混合性聋 未提及 CATSHL综合征 FGFR3 常显/常隐 先天到6岁 轻度到重度 SNHL 下降型 脊椎跖骨滑膜病综合征 FLNB 常显/常隐 2~10岁 中度到重度 SNHL/传导性聋/混合性聋 未提及 腓骨肌萎缩症1B型 MPZ 常显 儿童期到成年期 未提及 SNHL 未提及 腓骨肌萎缩症2C型 TRPV4 常显 35~62岁 轻度到重度 SNHL 下降/上升/U型 腓骨肌萎缩症4C型 SH3TC2 常隐 儿童期到25岁 轻度到重度 SNHL 未提及 腓骨肌萎缩症4H型 FDG4 常隐 15岁 轻度 SNHL 未提及 粘多糖病ⅣA型 GALNS 常隐 5岁 轻度到中度 SNHL 未提及 α-甘露糖苷贮积症 MAN2B1 常隐 未提及 中度到重度 SNHL 未提及 先天性垂体激素缺乏症3型 LHX3 常隐 未提及 轻度到极重度 SNHL 未提及 Alstrom综合征 ALMS1 常隐 儿童期 轻度到中度 SNHL 下降型 
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表 2 脊柱侧凸合并SNHL的典型病例的遗传信息总结
参考文献 综合征名称 基因 性别 年龄/岁 国籍 变异位点 Rose等[4] STL1 COL2A1 女 56 美国 p.Leu95fs*107 hemo STL1 COL2A1 男 35 美国 p.Gly322fs*345 hemo STL1 COL2A1 女 36 美国 p.Gly322fs*345 hemo STL1 COL2A1 女 30 美国 p.Arg333* hemo STL1 COL2A1 女 55 美国 p.Arg333* hemo STL1 COL2A1 男 70 美国 p.Arg732* hemo Lin等[12] 成骨不全症 COL1A1/COL1A2 女 31 中国 未提及 Pölsler等[14] Steel综合征 COL27A1 女 9 叙利亚 p.Phe32Leufs*71/p.Lys1026Argfs*33 Baumann等[15] Ehlers-Danlos综合征脊柱侧凸2型 FKBP14 男 16 奥地利 p.Glu122Argfs*7 homo Ehlers-Danlos综合征脊柱侧凸2型 FKBP14 女 48 奥地利 p.Glu122Argfs*7 homo Ehlers-Danlos综合征脊柱侧凸2型 FKBP14 女 11 意大利 p.Glu122Argfs*7 homo Ehlers-Danlos综合征脊柱侧凸2型 FKBP14 女 3 德国 p.Glu122Argfs*7/p.Thr15* Kosho等[19] EDS Kosho型 CHST14 女 16 日本 p.Pro281Leu/p.Tyr293Cys EDS Kosho型 CHST14 女 32 日本 p.Pro281Leu homo EDS Kosho型 CHST14 男 32 日本 p.Pro281Leu homo EDS Kosho型 CHST14 女 4 日本 p.Pro281Leu/p.Tyr293Cys Malfait等[18] EDS肌肉挛缩型 CHST14 女 22 土耳其 p.Val49* homo EDS肌肉挛缩型 CHST14 女 21 土耳其 p.Val49* homo Christensen等[20] EDSⅣB型 ZNF469 女 42 挪威 p.Cys3339Tyr homo EDSⅣB型 ZNF469 男 48 挪威 p.Cys3339Tyr homo Makrythanasis等[22] CATSHL综合征 FGFR3 女 14 埃及 p.Thr546Lys homo Krakow等[23] 脊椎跖骨滑膜病综合征 FLNB 女 5 美国 p.Arg649X homo Oonk等[28] 腓骨肌萎缩症2C型 TRPV4 男 38 荷兰 p.Arg269His hemo 腓骨肌萎缩症2C型 TRPV4 女 48 荷兰 p.Arg269His hemo 腓骨肌萎缩症2C型 TRPV4 女 68 荷兰 p.Arg269His hemo Lerat等[31] 腓骨肌萎缩症4C型 SH3TC2 女 22 法国 p.Arg954* homo 腓骨肌萎缩症4C型 SH3TC2 男 29 法国 p.Arg954* homo 腓骨肌萎缩症4C型 SH3TC2 男 56 法国 p.Tyr1107* homo 腓骨肌萎缩症4C型 SH3TC2 女 68 法国 p.Arg954* /p.Leu1126Pro 腓骨肌萎缩症4C型 SH3TC2 女 71 法国 p.Asn881Ser/p.Trp1199* 腓骨肌萎缩症4C型 SH3TC2 男 83 法国 p.Ala1206Asp homo Kondo等[32] 腓骨肌萎缩症4H型 FDG4 男 65 日本 p.Arg242* homo Xu等[33] 粘多糖病ⅣA型 GALNS 女 17 中国 p.Gly168Leu homo Malm等[34] α-甘露糖苷贮积症 MAN2B1 未提及 4 南非 未提及 Ramzan等[35] 先天性垂体激素缺乏症3型 LHX3 男 11 南非 p.Arg156* homo Liang等[37] Alstrom综合征 ALMS1 女 14 中国 p.Asn3150Lysfs2*/p.Val3154*fs
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