Table 1.
Description of the 11 patients included in the study, detailing all of the variants previously detected
| Patient | Phenotype | Other features | Gene | Identification | Genetic variant | Protein variant | Location | In silico prediction | cvg | Status |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | TCA (male) | Familial, non syndromic | RET | CS065611 | c.1263 + 2 T > A | - | 10:g.43604680 T > A; intronic | Splicing site | 268X | Detected |
| NTRK3 | rs139392904 | c.1933C > T | p.Arg645Cys | 15:g.88472622G > A; CDS | −/+ | 311X | Detected | |||
| EDN3 | rs11570344 | c.559_560insA | p.Glu187Glu | 20:g.57897443_57897444insA; CDS | Inframe insertion | 404X | Detected | |||
| 2 | L-HSCR (male) | Sporadic, non syndromic | SEMA3D | rs370785183 | c.1901G > A | p.Arg634Gln | 7:g.84636125C > T; CDS | −/+ | 90X | Detected |
| 3 | L-HSCR (male) | Sporadic, non syndromic | PROK1 | rs62623571 | c.142C > T | p.Arg48Trp | 1:g.110996652C > T; CDS | −/+ | 152X | Detected |
| 4 | S-HSCR (male) | Sporadic, non syndromic | RET | rs17158558 | c.2944C > T | p.Arg982Cys | 10:g.43620335C > T; CDS | −/+ | 146X | Detected |
| SOX10 | No | c.153delC | p.Gly52Alafs56Ter | 22:g.38379639delG; CDS | STOP gained | 46X | Detected | |||
| 5 | S-HSCR (male) | Sporadic, non syndromic | PROKR1 | rs373101730 | c.1063A > T | p.Lys354Asn | 2:g.68882589A > T; CDS | −/+ | 2332X | Detected |
| 6 | S-HSCR (male) | Sporadic, non syndromic | PSPN | rs199881560 | c.271C > T | p.Arg91Cys | 19:g.6375505G > A; CDS | +/+ | 13X | Detected |
| RET | CX065873 | c.1776G > A | p.Gly592Gly_Gly593Ter | 10:g.43609020GG > AT; CDS | STOP gained | 119X | Detected | |||
| 7 | TCA (male) | Sporadic, non syndromic | NTRK3 | No | c.1229 + 21delTCC | - | 15:g.88670477-79delGGA; intronic | Intronic | 105X | Detected |
| PROKR2 | rs78861628 | c.802C > T | p.Arg268Cys | 20:g.5283039G > A; CDS | +/+ | 5266X | Detected | |||
| 8 | L-HSCR (male) | Sporadic, non syndromic | NTF3 | rs1805149 | c.226G > A | p.Gly76Arg | 12:g.5603607G > A; CDS | −/− | 1247X | Detected |
| 9 | NA (male) | Sporadic, non syndromic | NRTN | No | c.199G > A | p.Ala67Thr | 19:g.5827789G > A; CDS | −/+ | 7X | Detected |
| NRTN | CM981393 | c.258 G > T | p.Ala96Ser | 19:g.5827876G > T; CDS | −/− | 0X | Not detected | |||
| 10 | L-HSCR (female) | Sporadic, non syndromic | PHOX2B | No | c.393_410del18bp(1) | p.Ala131_Leu136del | 4:g.41749386_41749404delGGTCGATCTTCAGGGCCA; CDS | Framehisft mutation | 163X | Detected |
| GDNF | rs36119840 | c.277C > T | p.Arg93Trp | 5:g.37816112G > A; CDS | +/+ | 704X | Detected | |||
| 11 | S-HSCR (male) | Sporadic, syndromic (X-linked hydrocephalus) | L1CAM | CM981156 | c.2077G > A | p.Gly693Arg | X:g.153132856C > T; CDS | +/+ | 221X | Detected |
TCA total colonic aganglionosis, L-HSCR long-segment HSCR, S-HSCR short-segment HSCR, NA not available data, Chr chromosome, cvg mean coverage, CDS coding DNA sequence
(1) c.93_410delGGTCGATCTTCAGGGCCA
In silico prediction: aminoacidic changes (−/−: benign for SIFT and Polyphen; −/+: damaging in one; +/+: damaging in both)