Table 2.
Genetic analysis for the 22 families with genetic diagnoses
| Family | Gene/Locus | Mutation | Inheritance | References (SNP)/novel | Exome sequencing | Sanger sequencing | Segregation of mutation |
|---|---|---|---|---|---|---|---|
| 930 | LMNA | NM_170707.3 c.832G>C, NP_733821.1 p.Ala278Pro hg19 chr1:156104999 | dominant | 8 | Proband (♂) | Proband | N/A |
| 1125 | LMNA | NM_170707.3 c.746G>A, NP_733821.1 p.Arg249Gln hg19 chr1:156104702 | de-novo dominant | 9 (rs59332535) | Proband (♂) | Trio | present in proband, absent in both parents |
| 965 | COL6A3 | NM_004369.3 c.4156G>A, NP_004360.2 p.Glu1386Lys hg19 chr2:238280504 | dominant | 11 | Proband (♂) | Proband | N/A |
| 1093 | COL6A3 | NM_004369.3 c.6283-1C>T hg19 chr2:238268032 | de-novo dominant, essential splice site | Novel | Proband (♀) and parents | Trio | present in proband, absent in both parents |
| 1115 | COL6A3 | NM_004369.3 c.6156+1G>A hg19 chr2:238270381 | de-novo dominant, essential splice site | 11 | Proband (♀) and parents | Trio | present in proband, absent in both parents |
| 1092 | COL6A1 | NM_001848.2 c.868G>A, NP_001839.2 p.Gly290Arg hg19 chr21:47409531 | de-novo dominant heterozygous | novel (rs121912939) [GeneDx, Emory Genetics laboratory] | Proband (♀) | Trio | present in proband, absent in both parents |
| 596 | RYR1 | NM_001042723.1 c.14567G>A, NP_001036188.1 p.Arg4856His hg19 chr19:39071080 | de-novo dominant | 12,13(rs63749869) | Proband (--) and parents | Trio | present in proband, absent in both parents |
| 1250 | VCP | NM_007126.3 c.572G>A, NP_009057.1 p.Arg191Gln hg19 chr9:35065252 | dominant heterozygous | 14 (rs121909334) | Proband (♂) | Proband and affected brother (1250-4) | present in both proband & affected brother |
| 1399 | FLNC | NM_001458.4 c.7409C>A, NP_001449.3 p.Pro2470His hg19 chr7:128496823 | dominant heterozygous | novel | Proband (♂) | Proband | N/A |
| 1090 | SMCHD1 | NM_015295.2 c.818_820del, NP_056110.2 p.Lys275del hg19 chr18:2688690_2688692del | dominant | 7 | Proband (♂), father | Proband, parents, brother (1–9) | |
| 1258 | D4Z4 | Deletion of D4Z4 repeats at 4q35 | heterozygous | Proband (♂) | Proband | N/A | |
| 1197 | CAPN3 | NM_000070.2 c.1465C>T, NP_000061.1 p.Arg489Trp hg19 chr15:42693949 and c.1715G>A, p.Arg572Gln hg19 chr15:42695170 | compound heterozygous |
15,16 as two separate mutations (rs121434544) |
Proband (♂) | Proband & affected sister | present in both proband & affected sister |
| 1365 | CAPN3 | NM_000070.2 c.945+5G>A hg19 chr15:42682299 and c.1746-20C>G hg9 chr15:42695919 | compound heterozygous affecting splicing | novel rs201892814 [Emory Genetics laboratory] |
Proband (♀) | Proband, unaffected father & affected brother | present only in proband & affected brother absent in unaffected father present in all three samples |
| 1049 | SGCG | NM_000231.2 c.195+4_195+7 del CAGTA>C hg19 chr13:23778027 and c.195+1G>C hg19 chr13:23778029 | compound heterozygous affecting splicing |
17 novel (rs200502077) |
Proband (♀), affected brother | Proband & affected brother | present in both proband & affected brother |
| 1118 | SGCG | NM_000231.2 c.787G>A, NP_000222.1 p.Glu263Lys hg19 chr13:23898591 | recessive homozygous | 38 (rs104894423) | Proband (♀) | Proband | N/A |
| 1299 | SGCA | NM_000023.2 c.109G>T, NP_000014.1 p.Val37Leu hg19 chr17:48244800 | consanguineous recessive homozygous | novel | Proband (♂) | Proband, parents, affected bro(−5) and unaffected sis(−4) | homozygous in proband & affected bro and heterozygous in parents and unaffected sis |
| 1102 | ANO5 | NM_213599.2 c.191dupA, NP_998764.1 p.Asn64Lys fs Ter15 hg19 chr11:22242653 | recessive homozygous | 18–20(rs137854521) | Proband (♂) | Proband | N/A |
| 1105 | ANO5 | NM_213599.2 c.191dupA, NP_998764.1 p.Asn64Lys fs Ter15 hg19 chr11:22242653 (exon 19) c.2235+5 G>A hg19 chr:22294540 | compound heterozygous | 18–20(rs137854521) novel | Proband (♂) | 1: proband; 2–3: parents 6: affected sister; 4, 5 &7: | heterozygous in 1, 3, 5 & 6; absent in 2, 4 & 7 heterozygous in 1, 2, 6, absent in 3, 4, 7 |
| 1395 | ANO5 | NM_213599.2 c.191dupA, NP_998764.1 p.Asn64Lys fs Ter15 hg19 chr11:22242653 and c.835C>T, p.Arg279Ter hg19 chr11:22261187 | compound heterozygous | 18–20(rs137854521) novel | Proband (♂) | 1, 2 & 4 | |
| 1117 | GAA | NM_000152.3 c.-32-13T>G r.spl hg19 chr17:78078341 and NM_000152.3 c.1841C>A, NP_000143.2 p.Thr614Lys hg19 chr17:78086463 | compound heterozygous | 28 (rs386834236) 27(rs369531647) | Proband (♂) | Proband | N/A |
| 1409 | LAMA2 | NM_000426.3 c.5116C>T, NP_000417.2 p.Arg1706Ter hg19 chr6:129712680 and c.8703+1G>A r.spl hg19 chr6:129826501 | compound heterozygous | 23 novel | Proband (♀) | Proband | N/A |
| 1107 | DMD | NM_004006.2 c.9G>A, NP_003997.1 p.Trp3Ter hg19 chrx:33229421 | X-linked non- sense | 29–31 | Proband (♂) | Proband | N/A |