Table 1 Clinical, laboratory, and genetic features of patients
Patient sex current age | Ethnic origin consanguinity | Age at onset (Gestational age) | Biopsied muscle Age at biopsy | Morphological methods (Functional studies) | Clinical phenotype | Permanent mechanical ventilation/age | NEB mutation: nucleotide/protein change | Effect of the mutations | Reference |
|---|---|---|---|---|---|---|---|---|---|
P1, F, deceased 10 days | French Caucasian, Yes | Antenatal (38 weeks) | Deltoid 2 days | IHC, IF, EM (Yes) | Group 1/Severe congenital nemaline myopathy Polyhydramnios, fœtal akinesia. Severe global hypotonia, respiratory distress, arthrogryposis, hip hyperlaxity, club feet and dysmorphic features. | Yes From birth | ex45; c.5574C > G; p.Tyr1858Stop; int122; c.19101 + 5G > A; p.Leu6333_Glu6367del | exon 45: nonsense mRNA decay (by RTPCR) exon 122: skipping confirmed by RTPCR and sequencing cDNA | Böhm et al., [15] |
P2, F, deceased at 1 month | French Jewish (Ashkenazi) Yes | Antenatal, (36 weeks) | Deltoid 5 days | IHC, EM (No) | Group 1/Severe congenital nemaline myopathy Polyhydramnios, fœtal akinesia. Severe global hypotonia, respiratory distress, arthrogryposis, club feet and dysmorphic features. | Yes From birth | homozygous deletion of exon 55 | Ashkenazi founder mutation; deletion of exon 55 | Lehtokari et al., [26] |
c.7432 + 1916_7535 + 372del p.Arg2478_Asp2512del | |||||||||
P3, M, deceased at 6 days | French Caucasian, No | Antenatal (38 weeks) | Deltoid 6 days | IHC, EM (No) | Group 1/Severe congenital nemaline myopathy Polyhydramnios, fœtal akinesia. Severe global hypotonia, respiratory distress, arthrogryposis, club feet, and dysmorphic features. | Yes From birth | ex86 (triplicated region); c.13066delT; p.Tyr4356Thrfs*8 ex110; c.17535G > A; p.Glu5845Glu | exon 86: frameshift mutation leading to either truncation or degradation. exon 110: splice site mutation | Present paper |
P4, M, deceased at 5 days, Brother of P5 | French Caucasian, Yes | Antenatal (29 weeks) | Vastus lateralis 3 days | IHC (No) | Group 1/Severe congenital nemaline myopathy Polyhydramnios, fœtal akinesia. Severe global hypotonia, absence of spontaneous movements at birth, respiratory distress, macrosomy and macrocephaly. | Yes From birth | ex177; c.24686_24687del; p.Glu8229Glufs*18 | both mutations truncating/degrading | |
ex163; c.23420_23421del; p.Arg7807Serfs*16 | |||||||||
P5, M, deceased at 29 days, Brother of P4 | French Caucasian, Yes | Antenatal (36 weeks) | Deltoid 15 days | IHC, EM (No) | Group 1/Severe congenital nemaline myopathy Polyhydramnios, macrosomy Severe global hypotonia, respiratory distress, reduced spontaneous movements, ptosis, arthrogryposis, hypetrichosis, and macrocephaly. | Yes From birth | ex177; c.24686_24687del; p.Glu8229Glufs*18 | both mutations truncating/degrading | |
ex163; c.23420_23421del; p.Arg7807Serfs*16 | |||||||||
P6, M, deceased at 5 months | French Caucasian, No | Birth (39 weeks) | Deltoid 9 weeks | IHC, IF, EM (No) | Group 2/Intermediate congenital nemaline myopathy Hypotonia and poor spontaneous movements at birth. At one month respiratory distress and deglutition problems. Elongated face. High-arched palate. Low-set ears. Facial diplegia. | Yes From 1 month | ex6; c.300dup; p.Tyr101fs*5 int49, c.6496-G > A, p.2166_2234del | exon 6: truncating/degrading exon 50 skiping by RT and cDNA sequencing | Present paper |
P7, F, deceased at 2 and half yrs | African, Yes | 11 days (39 weeks) | Vastus lateralis 6 months | IHC, IF, EM (Yes) | Group 2/Intermediate congenital nemaline myopathy. Apparently normal at birth. Successively hypotonia and deglutition problems. At 1.5 months development of progressive respiratory failure followed by recuperated cardiac arrest. | Yes From 2 months | homozygous 177; c.24735-24736DelA_fsx1 is this c.24735_24736del (AG) p.Arg8245fs*1 | truncating/degrading | Present paper |
P8, M 5 yrs | Argentinian, No | 6 months (40 weeks) | Vastus lateralis 6 months | IHC, EM (Yes) | Group 2/Intermediate congenital nemaline myopathy Hypotonia, motor delay. High-arched palate. Proximal and distal muscle weakness. Retractions of fingers. Mild hyperlaxity. At 1 year development of progressive respiratory involvement necessitating tracheostomy. | Yes From 1 month | ex139; c.20928G > T; p.Gly6976Gly | RTPCR and Sanger sequencing of cDNA showed that instead of 105 nt, exon 139 contains only 34 nt: frameshift and a premature stop codon. Exon 172; truncating/degrading | Present paper |
ex172; c.24269del p.Arg8090fs*54 | |||||||||
P9, M, 11 yrs | French Caucasian, Yes | Birth (39 weeks) | Deltoid 10 months | IHC, IF, EM (Yes) | Group 2/Intermediate congenital nemaline myopathy Shortly after birth severe respiratory failure. Tracheostomy and gastrostomy at five months. Facial diplegia, drooling, deglutition problems. Axial hypotonia and weakness of all limb muscles. | Yes From 5 months | homozygous ex174; c.24440_24441insGTCA, p.Pro8148Serfs*15 | truncating/degrading | Present paper |
P10, M, 17 yrs | French Caucasian, No | 6 years (At term) | Deltoid 6 years | IHC, IF, EM (Yes) | Group 3/Typical congenital nemaline myopathy. Global hypotonia, deglutition problems. Proximal muscle weakness. Facial diplegia. Nasal voice. Mild respiratory insufficiency treated with discontinuous non-invasive ventilation. | No | int43; c.5343 + 5G > A p.Arg1747_Thr1778del ex153; c.22273del p.Val7425Serfs49* | intron 43: a splice site mutation exon153: truncating/degrading | Present paper |
P11, M, 19 years | French Antillean No | 1 yrs (At term) | Vastus lateralis 6 yrs | IHC, IF, EM (Yes) | Group 3/Typical congenital nemaline myopathy. Hypotonia and feeding difficulties. Delayed motor milestones. Facial weakness with open mouth. Axial and limb girdle proximal weakness. Mild respiratory involvement treated with discontinuous non-invasive ventilation. | No | ex175; c.24579G > A, p.Ser8193Ser ex119; c.18676C > T, p.Gln6226* | ex175: a splice site mutation ex119: a nonsense mutation (truncating/degrading) | Present paper |
P12, M, 20 yrs | French Caucasian, No | 2-3 years (At term) | Vastus lateralis 6 years | IHC, EM (No) | Group 3/Typical congenital nemaline myopathy. Difficulties in running and rising stairs. Facial weakness with open mouth. Mild upper and lower limb girdle weakness. | No | int155; c.22591-3C > G; p.7531Val_Ser7564del; ex148; c.21796_21810delinsT; p.Pro7266fs*30 | intron 155: a splice site mutation exon 148: truncating/degrading | Present paper |
P13, F, 52 yrs | French Caucasian, No | 6 yrs (At term) | Deltoid 18 years | IHC, EM (No) | Group 3/Mild congenital nemaline myopathy. Difficulties in sport activities in school. Bilateral pes cavus. Presence of mild upper girdle musle weakness. Diffuse muscle pain. | No | ex69; c.10043_10046del, p.Val3348Alafs *43 ex49; c.6388G > C p.Ala2130Pro | ex69: truncating/degrading ex49: missense on the acting binding site | Present paper |
P14, F, 37 yrs | French Caucasian, No | 2 yrs (At term) | Deltoid 21 yrs | IHC, IF, EM (Yes) | Group 3/Mild congenital nemaline myopathy. Frequent falls. Difficulties in running , rising stairs. Jaw contractures. Nasal voice. Elongated face. Respiratory involvement. Axial weakness with difficulties in neck flexion. Asymmentrical distal weaakness with foot drop (right > left). Proximo-distal weakness. | No | int17; c.1569 + 1G > A p.His491_Asp523del | intron 17: a splice site mutation | Present paper |
exon 176: truncating/degrading | |||||||||
ex176; c.24606del p.Ala8203Glnfs*13 |