Table 2.
RPL5 Mutations in 18 Probands and Six Family Members from a Total of 196 Families Studied
| Mutation Type | Proband's ID (Gender) Inheritance | Family Members | DNA Mutation | Exon/ Intron | Predicted Amino Acid Change | Age at Diagosis | Malformation Status | Response at First Steroid Therapy | Present Therapy |
|---|---|---|---|---|---|---|---|---|---|
| Nonsense mutation | P1 (F) sporadic | m: normal seq | c.48C→G | Ex2 | Y16Stop | at birth | NA | responsive to high doses only | RBC trx |
| P2 (F) de novo | f, m: normal seq | c.67C→T | Ex2 | R23Stop | 2mo | cleft lip, cleft palate | responsive SD | RBC trx | |
| P3 (F) sporadic | c.228C→A | Ex4 | C76Stop | 10 mo | cleft palate, ASD, hypoplastic thumb, micrognathia, tracheomalacia | initially responsive | stem cell transplant | ||
| Missense mutation | P4 (M) familial | m, s, b: normal seq | c.418G→A | Ex5 | G140S | 3 mo | none | unresponsive | RBC trx |
| f | c.418G→A | Ex5 | G140S | no anemia | NA | no therapy | no therapy | ||
| Deletion/ insertion | P5 (M) sporadic | c.46_47 insA | Ex2 | Y16Stop | at birth | micrognathia, hypertelorism, soft cleft palate, triphalangeal right thumb, widened webbed spaced between first and second toes, hypospadias | no therapy | no therapy | |
| P6 (F) de novo | f, m: normal seq | c.156_159 delAGTT | Ex3 | Frameshift at codon 52; stop at 54 | 10 mo | small jaw, cleft palate, triphlangeal thumb, hip dysplasia, rib anomalies | responsive SD | steroid therapy | |
| P7 (M) sporadic | c.169_172 delAACA | Ex3 | Frameshift at codon 57; stop at 68 | at birth | partial anomalous pulmonary venous return | unresponsive | RBC trx | ||
| P8 (M) de novo | f, m, b: normal seq | c.173 delG | Ex3 | Frameshift at codon 58; stop at 69 | 9 mo | multiple congenital heart defectsa | responsive SD | RBC trx | |
| P9 (M) sporadic | c.173_4 delGA | Ex3 | Frameshift at codon 58; stop at 111 | NA | long proximal thumb phalanges bilateral, multiple congenital heart defectsb | NA | NA | ||
| P10 (M) sporadic | c.173_4 delGA | Ex3 | Frameshift at codon 58; stop at 111 | 10 mo | small jaw, cleft palate, bronchiopharyngeal malacia, mild hydrocephalus | responsive SD | steroid therapy | ||
| P11 (F) de novo | f, m, b, s: normal seq | c.173_4 delGA | Ex3 | Frameshift at codon 58; stop at 111 | NA | NA | NA | NA | |
| P12 (F) familial | c.235_236 insT | EX4 | Frameshift at codon 79; stop at 112 | 11 yc | cleft soft palate | unresponsive | RBC trx | ||
| m: familial | c.235_236 insT | EX4 | Frameshift at codon 79; stop at 112 | 55 y | none | refused steroid trial | RBC trx | ||
| P13 (F) familial | c.235_236 insT | EX4 | Frameshift at codon 79; stop at 112 | 12 mo | cleft palate, bifid uvula, hypoplastic thumb, | NA | RBC trx | ||
| m: familial | c.235_236 insT | EX4 | Frameshift at codon 79; stop at 112 | NA | none | NA | RBC trx | ||
| P14 (F) familial | 348_351 insTGGA | Ex5 | Frameshift at codon 117; stop at 121 | 12 mo | mandibular hypoplasia with retrognathia, cleft palate with bifid uvula, dysplastic thumbs, ASD type II | unresponsive | RBC trx | ||
| s: familial | ND | ND | 12 mo | mandibular hypoplasia with retrognathia, cleft palate, triphalangeal thumbs, persistent foramen ovale, ASD type II | no therapy | no therapy | |||
| m: familial | 348_351 insTGGA | Ex5 | Frameshift at codon 117; stop at 121 | 20 yr | none | no therapy | no therapy | ||
| P15 (M) familial | f, m, s: normal seq | c.498_502 delTGTGG and 39bp ins | Ex5 | NA | triphalangeal thumbs, VSD | responsive | no therapy | ||
| b: familial | c.498_502 delTGTGG and 39bp ins | Ex5 | NA | cleft lip, triphalangeal thumbs | unresponsive | RBC trx | |||
| d: familial | c.498_502 delTGTGG and 39bp ins | Ex5 | NA | NA | NA | NA | |||
| P16 (M) sporadic | c.573_574 insG | Ex. 6 | Frameshift at codon 192; stop at 216 | NA | inability to flex right distal thumb phalanx | responsive SD | NA | ||
| Splice-site mutation | P17 (M) de novo | f, m, b: normal seq | Donor splice site IVS2 +2t→g | Intr2 | NA | none | responsive SD | RBC trx | |
| P18 (M) sporadic | Donor splice site IVS3 +1g→t | Intr3 | NA | none | responsive SD | RBC trx |
Abbreviations are as follows: P, proband; f, father; m, mother; s, sister; b, brother; d, daughter; ins, insertion; del, deletion; Ex, exon; In, intron; seq, sequence; mo, month; y, years; ND, not done; NA, not available; SD, steroid dependent; RBC trx, red blood cell transfusions; ASD, atrial septal defect; VSD, ventricular septal defect.
a
Small patent ductus arteriosus, mild mitral valve prolapse, mild mitral regurgitation.
b
Double outlet right ventricle, pulmonary stenosis, left pulmonary artery stenosis, patent ductus arteriosus.
c
macrocytic anemia diagnosed at age 11, DBA not diagnosed until years later.