Muscle and bone characteristics of a Chinese family with spinal muscular atrophy, lower extremity predominant 1 (SMALED1) caused by a novel missense DYNC1H1 mutation

Background Spinal muscular atrophy, lower extremity predominant (SMALED) is a type of non-5q spinal muscular atrophy characterised by weakness and atrophy of lower limb muscles without sensory abnormalities. SMALED1 can be caused by dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene variants. However...
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Autor*in:	Mei, Yazhao [verfasserIn] Jiang, Yunyi Zhang, Zhenlin Zhang, Hao

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	SMALED1 Whole-exome sequencing Sanger sequencing Bone metabolism

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: BMC medical genomics - London : BioMed Central, 2008, 16(2023), 1 vom: 07. März
Übergeordnetes Werk:	volume:16 ; year:2023 ; number:1 ; day:07 ; month:03

Links:	Volltext

DOI / URN:	10.1186/s12920-023-01472-4

Katalog-ID:	SPR051538377

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520			\|a Background Spinal muscular atrophy, lower extremity predominant (SMALED) is a type of non-5q spinal muscular atrophy characterised by weakness and atrophy of lower limb muscles without sensory abnormalities. SMALED1 can be caused by dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene variants. However, the phenotype and genotype of SMALED1 may overlap with those of other neuromuscular diseases, making it difficult to diagnose clinically. Additionally, bone metabolism and bone mineral density (BMD) in patients with SMALED1 have never been reported. Methods We investigated a Chinese family in which 5 individuals from 3 generations had lower limb muscle atrophy and foot deformities. Clinical manifestations and biochemical and radiographic indices were analysed, and mutational analysis was performed by whole-exome sequencing (WES) and Sanger sequencing. Results A novel mutation in exon 4 of the DYNC1H1 gene (c.587T > C, p.Leu196Ser) was identified in the proband and his affected mother by WES. Sanger sequencing confirmed that the proband and 3 affected family members were carriers of this mutation. As leucine is a hydrophobic amino acid and serine is hydrophilic, the hydrophobic interaction resulting from mutation of amino acid residue 196 could influence the stability of the DYNC1H1 protein. Leg muscle magnetic resonance imaging of the proband revealed severe atrophy and fatty infiltration, and electromyographic recordings showed chronic neurogenic impairment of the lower extremities. Bone metabolism markers and BMD of the proband were all within normal ranges. None of the 4 patients had experienced fragility fractures. Conclusion This study identified a novel DYNC1H1 mutation and expands the spectrum of phenotypes and genotypes of DYNC1H1-related disorders. This is the first report of bone metabolism and BMD in patients with SMALED1.
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allfields	10.1186/s12920-023-01472-4 doi (DE-627)SPR051538377 (SPR)s12920-023-01472-4-e DE-627 ger DE-627 rakwb eng Mei, Yazhao verfasserin aut Muscle and bone characteristics of a Chinese family with spinal muscular atrophy, lower extremity predominant 1 (SMALED1) caused by a novel missense DYNC1H1 mutation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Spinal muscular atrophy, lower extremity predominant (SMALED) is a type of non-5q spinal muscular atrophy characterised by weakness and atrophy of lower limb muscles without sensory abnormalities. SMALED1 can be caused by dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene variants. However, the phenotype and genotype of SMALED1 may overlap with those of other neuromuscular diseases, making it difficult to diagnose clinically. Additionally, bone metabolism and bone mineral density (BMD) in patients with SMALED1 have never been reported. Methods We investigated a Chinese family in which 5 individuals from 3 generations had lower limb muscle atrophy and foot deformities. Clinical manifestations and biochemical and radiographic indices were analysed, and mutational analysis was performed by whole-exome sequencing (WES) and Sanger sequencing. Results A novel mutation in exon 4 of the DYNC1H1 gene (c.587T > C, p.Leu196Ser) was identified in the proband and his affected mother by WES. Sanger sequencing confirmed that the proband and 3 affected family members were carriers of this mutation. As leucine is a hydrophobic amino acid and serine is hydrophilic, the hydrophobic interaction resulting from mutation of amino acid residue 196 could influence the stability of the DYNC1H1 protein. Leg muscle magnetic resonance imaging of the proband revealed severe atrophy and fatty infiltration, and electromyographic recordings showed chronic neurogenic impairment of the lower extremities. Bone metabolism markers and BMD of the proband were all within normal ranges. None of the 4 patients had experienced fragility fractures. Conclusion This study identified a novel DYNC1H1 mutation and expands the spectrum of phenotypes and genotypes of DYNC1H1-related disorders. This is the first report of bone metabolism and BMD in patients with SMALED1. SMALED1 (dpeaa)DE-He213 Whole-exome sequencing (dpeaa)DE-He213 Sanger sequencing (dpeaa)DE-He213 Bone metabolism (dpeaa)DE-He213 Jiang, Yunyi aut Zhang, Zhenlin aut Zhang, Hao aut Enthalten in BMC medical genomics London : BioMed Central, 2008 16(2023), 1 vom: 07. März (DE-627)559080824 (DE-600)2411865-5 1755-8794 nnns volume:16 year:2023 number:1 day:07 month:03 https://dx.doi.org/10.1186/s12920-023-01472-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2023 1 07 03
spelling	10.1186/s12920-023-01472-4 doi (DE-627)SPR051538377 (SPR)s12920-023-01472-4-e DE-627 ger DE-627 rakwb eng Mei, Yazhao verfasserin aut Muscle and bone characteristics of a Chinese family with spinal muscular atrophy, lower extremity predominant 1 (SMALED1) caused by a novel missense DYNC1H1 mutation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Spinal muscular atrophy, lower extremity predominant (SMALED) is a type of non-5q spinal muscular atrophy characterised by weakness and atrophy of lower limb muscles without sensory abnormalities. SMALED1 can be caused by dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene variants. However, the phenotype and genotype of SMALED1 may overlap with those of other neuromuscular diseases, making it difficult to diagnose clinically. Additionally, bone metabolism and bone mineral density (BMD) in patients with SMALED1 have never been reported. Methods We investigated a Chinese family in which 5 individuals from 3 generations had lower limb muscle atrophy and foot deformities. Clinical manifestations and biochemical and radiographic indices were analysed, and mutational analysis was performed by whole-exome sequencing (WES) and Sanger sequencing. Results A novel mutation in exon 4 of the DYNC1H1 gene (c.587T > C, p.Leu196Ser) was identified in the proband and his affected mother by WES. Sanger sequencing confirmed that the proband and 3 affected family members were carriers of this mutation. As leucine is a hydrophobic amino acid and serine is hydrophilic, the hydrophobic interaction resulting from mutation of amino acid residue 196 could influence the stability of the DYNC1H1 protein. Leg muscle magnetic resonance imaging of the proband revealed severe atrophy and fatty infiltration, and electromyographic recordings showed chronic neurogenic impairment of the lower extremities. Bone metabolism markers and BMD of the proband were all within normal ranges. None of the 4 patients had experienced fragility fractures. Conclusion This study identified a novel DYNC1H1 mutation and expands the spectrum of phenotypes and genotypes of DYNC1H1-related disorders. This is the first report of bone metabolism and BMD in patients with SMALED1. SMALED1 (dpeaa)DE-He213 Whole-exome sequencing (dpeaa)DE-He213 Sanger sequencing (dpeaa)DE-He213 Bone metabolism (dpeaa)DE-He213 Jiang, Yunyi aut Zhang, Zhenlin aut Zhang, Hao aut Enthalten in BMC medical genomics London : BioMed Central, 2008 16(2023), 1 vom: 07. März (DE-627)559080824 (DE-600)2411865-5 1755-8794 nnns volume:16 year:2023 number:1 day:07 month:03 https://dx.doi.org/10.1186/s12920-023-01472-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2023 1 07 03
allfields_unstemmed	10.1186/s12920-023-01472-4 doi (DE-627)SPR051538377 (SPR)s12920-023-01472-4-e DE-627 ger DE-627 rakwb eng Mei, Yazhao verfasserin aut Muscle and bone characteristics of a Chinese family with spinal muscular atrophy, lower extremity predominant 1 (SMALED1) caused by a novel missense DYNC1H1 mutation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Spinal muscular atrophy, lower extremity predominant (SMALED) is a type of non-5q spinal muscular atrophy characterised by weakness and atrophy of lower limb muscles without sensory abnormalities. SMALED1 can be caused by dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene variants. However, the phenotype and genotype of SMALED1 may overlap with those of other neuromuscular diseases, making it difficult to diagnose clinically. Additionally, bone metabolism and bone mineral density (BMD) in patients with SMALED1 have never been reported. Methods We investigated a Chinese family in which 5 individuals from 3 generations had lower limb muscle atrophy and foot deformities. Clinical manifestations and biochemical and radiographic indices were analysed, and mutational analysis was performed by whole-exome sequencing (WES) and Sanger sequencing. Results A novel mutation in exon 4 of the DYNC1H1 gene (c.587T > C, p.Leu196Ser) was identified in the proband and his affected mother by WES. Sanger sequencing confirmed that the proband and 3 affected family members were carriers of this mutation. As leucine is a hydrophobic amino acid and serine is hydrophilic, the hydrophobic interaction resulting from mutation of amino acid residue 196 could influence the stability of the DYNC1H1 protein. Leg muscle magnetic resonance imaging of the proband revealed severe atrophy and fatty infiltration, and electromyographic recordings showed chronic neurogenic impairment of the lower extremities. Bone metabolism markers and BMD of the proband were all within normal ranges. None of the 4 patients had experienced fragility fractures. Conclusion This study identified a novel DYNC1H1 mutation and expands the spectrum of phenotypes and genotypes of DYNC1H1-related disorders. This is the first report of bone metabolism and BMD in patients with SMALED1. SMALED1 (dpeaa)DE-He213 Whole-exome sequencing (dpeaa)DE-He213 Sanger sequencing (dpeaa)DE-He213 Bone metabolism (dpeaa)DE-He213 Jiang, Yunyi aut Zhang, Zhenlin aut Zhang, Hao aut Enthalten in BMC medical genomics London : BioMed Central, 2008 16(2023), 1 vom: 07. März (DE-627)559080824 (DE-600)2411865-5 1755-8794 nnns volume:16 year:2023 number:1 day:07 month:03 https://dx.doi.org/10.1186/s12920-023-01472-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2023 1 07 03
allfieldsGer	10.1186/s12920-023-01472-4 doi (DE-627)SPR051538377 (SPR)s12920-023-01472-4-e DE-627 ger DE-627 rakwb eng Mei, Yazhao verfasserin aut Muscle and bone characteristics of a Chinese family with spinal muscular atrophy, lower extremity predominant 1 (SMALED1) caused by a novel missense DYNC1H1 mutation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Spinal muscular atrophy, lower extremity predominant (SMALED) is a type of non-5q spinal muscular atrophy characterised by weakness and atrophy of lower limb muscles without sensory abnormalities. SMALED1 can be caused by dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene variants. However, the phenotype and genotype of SMALED1 may overlap with those of other neuromuscular diseases, making it difficult to diagnose clinically. Additionally, bone metabolism and bone mineral density (BMD) in patients with SMALED1 have never been reported. Methods We investigated a Chinese family in which 5 individuals from 3 generations had lower limb muscle atrophy and foot deformities. Clinical manifestations and biochemical and radiographic indices were analysed, and mutational analysis was performed by whole-exome sequencing (WES) and Sanger sequencing. Results A novel mutation in exon 4 of the DYNC1H1 gene (c.587T > C, p.Leu196Ser) was identified in the proband and his affected mother by WES. Sanger sequencing confirmed that the proband and 3 affected family members were carriers of this mutation. As leucine is a hydrophobic amino acid and serine is hydrophilic, the hydrophobic interaction resulting from mutation of amino acid residue 196 could influence the stability of the DYNC1H1 protein. Leg muscle magnetic resonance imaging of the proband revealed severe atrophy and fatty infiltration, and electromyographic recordings showed chronic neurogenic impairment of the lower extremities. Bone metabolism markers and BMD of the proband were all within normal ranges. None of the 4 patients had experienced fragility fractures. Conclusion This study identified a novel DYNC1H1 mutation and expands the spectrum of phenotypes and genotypes of DYNC1H1-related disorders. This is the first report of bone metabolism and BMD in patients with SMALED1. SMALED1 (dpeaa)DE-He213 Whole-exome sequencing (dpeaa)DE-He213 Sanger sequencing (dpeaa)DE-He213 Bone metabolism (dpeaa)DE-He213 Jiang, Yunyi aut Zhang, Zhenlin aut Zhang, Hao aut Enthalten in BMC medical genomics London : BioMed Central, 2008 16(2023), 1 vom: 07. März (DE-627)559080824 (DE-600)2411865-5 1755-8794 nnns volume:16 year:2023 number:1 day:07 month:03 https://dx.doi.org/10.1186/s12920-023-01472-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2023 1 07 03
allfieldsSound	10.1186/s12920-023-01472-4 doi (DE-627)SPR051538377 (SPR)s12920-023-01472-4-e DE-627 ger DE-627 rakwb eng Mei, Yazhao verfasserin aut Muscle and bone characteristics of a Chinese family with spinal muscular atrophy, lower extremity predominant 1 (SMALED1) caused by a novel missense DYNC1H1 mutation 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Spinal muscular atrophy, lower extremity predominant (SMALED) is a type of non-5q spinal muscular atrophy characterised by weakness and atrophy of lower limb muscles without sensory abnormalities. SMALED1 can be caused by dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene variants. However, the phenotype and genotype of SMALED1 may overlap with those of other neuromuscular diseases, making it difficult to diagnose clinically. Additionally, bone metabolism and bone mineral density (BMD) in patients with SMALED1 have never been reported. Methods We investigated a Chinese family in which 5 individuals from 3 generations had lower limb muscle atrophy and foot deformities. Clinical manifestations and biochemical and radiographic indices were analysed, and mutational analysis was performed by whole-exome sequencing (WES) and Sanger sequencing. Results A novel mutation in exon 4 of the DYNC1H1 gene (c.587T > C, p.Leu196Ser) was identified in the proband and his affected mother by WES. Sanger sequencing confirmed that the proband and 3 affected family members were carriers of this mutation. As leucine is a hydrophobic amino acid and serine is hydrophilic, the hydrophobic interaction resulting from mutation of amino acid residue 196 could influence the stability of the DYNC1H1 protein. Leg muscle magnetic resonance imaging of the proband revealed severe atrophy and fatty infiltration, and electromyographic recordings showed chronic neurogenic impairment of the lower extremities. Bone metabolism markers and BMD of the proband were all within normal ranges. None of the 4 patients had experienced fragility fractures. Conclusion This study identified a novel DYNC1H1 mutation and expands the spectrum of phenotypes and genotypes of DYNC1H1-related disorders. This is the first report of bone metabolism and BMD in patients with SMALED1. SMALED1 (dpeaa)DE-He213 Whole-exome sequencing (dpeaa)DE-He213 Sanger sequencing (dpeaa)DE-He213 Bone metabolism (dpeaa)DE-He213 Jiang, Yunyi aut Zhang, Zhenlin aut Zhang, Hao aut Enthalten in BMC medical genomics London : BioMed Central, 2008 16(2023), 1 vom: 07. März (DE-627)559080824 (DE-600)2411865-5 1755-8794 nnns volume:16 year:2023 number:1 day:07 month:03 https://dx.doi.org/10.1186/s12920-023-01472-4 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2023 1 07 03
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SMALED1 can be caused by dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene variants. However, the phenotype and genotype of SMALED1 may overlap with those of other neuromuscular diseases, making it difficult to diagnose clinically. Additionally, bone metabolism and bone mineral density (BMD) in patients with SMALED1 have never been reported. Methods We investigated a Chinese family in which 5 individuals from 3 generations had lower limb muscle atrophy and foot deformities. Clinical manifestations and biochemical and radiographic indices were analysed, and mutational analysis was performed by whole-exome sequencing (WES) and Sanger sequencing. Results A novel mutation in exon 4 of the DYNC1H1 gene (c.587T > C, p.Leu196Ser) was identified in the proband and his affected mother by WES. Sanger sequencing confirmed that the proband and 3 affected family members were carriers of this mutation. As leucine is a hydrophobic amino acid and serine is hydrophilic, the hydrophobic interaction resulting from mutation of amino acid residue 196 could influence the stability of the DYNC1H1 protein. Leg muscle magnetic resonance imaging of the proband revealed severe atrophy and fatty infiltration, and electromyographic recordings showed chronic neurogenic impairment of the lower extremities. Bone metabolism markers and BMD of the proband were all within normal ranges. None of the 4 patients had experienced fragility fractures. Conclusion This study identified a novel DYNC1H1 mutation and expands the spectrum of phenotypes and genotypes of DYNC1H1-related disorders. 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author	Mei, Yazhao
spellingShingle	Mei, Yazhao misc SMALED1 misc Whole-exome sequencing misc Sanger sequencing misc Bone metabolism Muscle and bone characteristics of a Chinese family with spinal muscular atrophy, lower extremity predominant 1 (SMALED1) caused by a novel missense DYNC1H1 mutation
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topic_title	Muscle and bone characteristics of a Chinese family with spinal muscular atrophy, lower extremity predominant 1 (SMALED1) caused by a novel missense DYNC1H1 mutation SMALED1 (dpeaa)DE-He213 Whole-exome sequencing (dpeaa)DE-He213 Sanger sequencing (dpeaa)DE-He213 Bone metabolism (dpeaa)DE-He213
topic	misc SMALED1 misc Whole-exome sequencing misc Sanger sequencing misc Bone metabolism
topic_unstemmed	misc SMALED1 misc Whole-exome sequencing misc Sanger sequencing misc Bone metabolism
topic_browse	misc SMALED1 misc Whole-exome sequencing misc Sanger sequencing misc Bone metabolism
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title	Muscle and bone characteristics of a Chinese family with spinal muscular atrophy, lower extremity predominant 1 (SMALED1) caused by a novel missense DYNC1H1 mutation
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title_full	Muscle and bone characteristics of a Chinese family with spinal muscular atrophy, lower extremity predominant 1 (SMALED1) caused by a novel missense DYNC1H1 mutation
author_sort	Mei, Yazhao
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author_browse	Mei, Yazhao Jiang, Yunyi Zhang, Zhenlin Zhang, Hao
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title_sort	muscle and bone characteristics of a chinese family with spinal muscular atrophy, lower extremity predominant 1 (smaled1) caused by a novel missense dync1h1 mutation
title_auth	Muscle and bone characteristics of a Chinese family with spinal muscular atrophy, lower extremity predominant 1 (SMALED1) caused by a novel missense DYNC1H1 mutation
abstract	Background Spinal muscular atrophy, lower extremity predominant (SMALED) is a type of non-5q spinal muscular atrophy characterised by weakness and atrophy of lower limb muscles without sensory abnormalities. SMALED1 can be caused by dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene variants. However, the phenotype and genotype of SMALED1 may overlap with those of other neuromuscular diseases, making it difficult to diagnose clinically. Additionally, bone metabolism and bone mineral density (BMD) in patients with SMALED1 have never been reported. Methods We investigated a Chinese family in which 5 individuals from 3 generations had lower limb muscle atrophy and foot deformities. Clinical manifestations and biochemical and radiographic indices were analysed, and mutational analysis was performed by whole-exome sequencing (WES) and Sanger sequencing. Results A novel mutation in exon 4 of the DYNC1H1 gene (c.587T > C, p.Leu196Ser) was identified in the proband and his affected mother by WES. Sanger sequencing confirmed that the proband and 3 affected family members were carriers of this mutation. As leucine is a hydrophobic amino acid and serine is hydrophilic, the hydrophobic interaction resulting from mutation of amino acid residue 196 could influence the stability of the DYNC1H1 protein. Leg muscle magnetic resonance imaging of the proband revealed severe atrophy and fatty infiltration, and electromyographic recordings showed chronic neurogenic impairment of the lower extremities. Bone metabolism markers and BMD of the proband were all within normal ranges. None of the 4 patients had experienced fragility fractures. Conclusion This study identified a novel DYNC1H1 mutation and expands the spectrum of phenotypes and genotypes of DYNC1H1-related disorders. This is the first report of bone metabolism and BMD in patients with SMALED1. © The Author(s) 2023
abstractGer	Background Spinal muscular atrophy, lower extremity predominant (SMALED) is a type of non-5q spinal muscular atrophy characterised by weakness and atrophy of lower limb muscles without sensory abnormalities. SMALED1 can be caused by dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene variants. However, the phenotype and genotype of SMALED1 may overlap with those of other neuromuscular diseases, making it difficult to diagnose clinically. Additionally, bone metabolism and bone mineral density (BMD) in patients with SMALED1 have never been reported. Methods We investigated a Chinese family in which 5 individuals from 3 generations had lower limb muscle atrophy and foot deformities. Clinical manifestations and biochemical and radiographic indices were analysed, and mutational analysis was performed by whole-exome sequencing (WES) and Sanger sequencing. Results A novel mutation in exon 4 of the DYNC1H1 gene (c.587T > C, p.Leu196Ser) was identified in the proband and his affected mother by WES. Sanger sequencing confirmed that the proband and 3 affected family members were carriers of this mutation. As leucine is a hydrophobic amino acid and serine is hydrophilic, the hydrophobic interaction resulting from mutation of amino acid residue 196 could influence the stability of the DYNC1H1 protein. Leg muscle magnetic resonance imaging of the proband revealed severe atrophy and fatty infiltration, and electromyographic recordings showed chronic neurogenic impairment of the lower extremities. Bone metabolism markers and BMD of the proband were all within normal ranges. None of the 4 patients had experienced fragility fractures. Conclusion This study identified a novel DYNC1H1 mutation and expands the spectrum of phenotypes and genotypes of DYNC1H1-related disorders. This is the first report of bone metabolism and BMD in patients with SMALED1. © The Author(s) 2023
abstract_unstemmed	Background Spinal muscular atrophy, lower extremity predominant (SMALED) is a type of non-5q spinal muscular atrophy characterised by weakness and atrophy of lower limb muscles without sensory abnormalities. SMALED1 can be caused by dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene variants. However, the phenotype and genotype of SMALED1 may overlap with those of other neuromuscular diseases, making it difficult to diagnose clinically. Additionally, bone metabolism and bone mineral density (BMD) in patients with SMALED1 have never been reported. Methods We investigated a Chinese family in which 5 individuals from 3 generations had lower limb muscle atrophy and foot deformities. Clinical manifestations and biochemical and radiographic indices were analysed, and mutational analysis was performed by whole-exome sequencing (WES) and Sanger sequencing. Results A novel mutation in exon 4 of the DYNC1H1 gene (c.587T > C, p.Leu196Ser) was identified in the proband and his affected mother by WES. Sanger sequencing confirmed that the proband and 3 affected family members were carriers of this mutation. As leucine is a hydrophobic amino acid and serine is hydrophilic, the hydrophobic interaction resulting from mutation of amino acid residue 196 could influence the stability of the DYNC1H1 protein. Leg muscle magnetic resonance imaging of the proband revealed severe atrophy and fatty infiltration, and electromyographic recordings showed chronic neurogenic impairment of the lower extremities. Bone metabolism markers and BMD of the proband were all within normal ranges. None of the 4 patients had experienced fragility fractures. Conclusion This study identified a novel DYNC1H1 mutation and expands the spectrum of phenotypes and genotypes of DYNC1H1-related disorders. This is the first report of bone metabolism and BMD in patients with SMALED1. © The Author(s) 2023
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title_short	Muscle and bone characteristics of a Chinese family with spinal muscular atrophy, lower extremity predominant 1 (SMALED1) caused by a novel missense DYNC1H1 mutation
url	https://dx.doi.org/10.1186/s12920-023-01472-4
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up_date	2024-07-03T22:22:49.459Z
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SMALED1 can be caused by dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene variants. However, the phenotype and genotype of SMALED1 may overlap with those of other neuromuscular diseases, making it difficult to diagnose clinically. Additionally, bone metabolism and bone mineral density (BMD) in patients with SMALED1 have never been reported. Methods We investigated a Chinese family in which 5 individuals from 3 generations had lower limb muscle atrophy and foot deformities. Clinical manifestations and biochemical and radiographic indices were analysed, and mutational analysis was performed by whole-exome sequencing (WES) and Sanger sequencing. Results A novel mutation in exon 4 of the DYNC1H1 gene (c.587T > C, p.Leu196Ser) was identified in the proband and his affected mother by WES. Sanger sequencing confirmed that the proband and 3 affected family members were carriers of this mutation. As leucine is a hydrophobic amino acid and serine is hydrophilic, the hydrophobic interaction resulting from mutation of amino acid residue 196 could influence the stability of the DYNC1H1 protein. Leg muscle magnetic resonance imaging of the proband revealed severe atrophy and fatty infiltration, and electromyographic recordings showed chronic neurogenic impairment of the lower extremities. Bone metabolism markers and BMD of the proband were all within normal ranges. None of the 4 patients had experienced fragility fractures. Conclusion This study identified a novel DYNC1H1 mutation and expands the spectrum of phenotypes and genotypes of DYNC1H1-related disorders. 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Muscle and bone characteristics of a Chinese family with spinal muscular atrophy, lower extremity predominant 1 (SMALED1) caused by a novel missense DYNC1H1 mutation

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