Table 2.
Genetic variants, phenotype, and family history of 21 patients with membrane disorders
| Patient | Previous diagnosis | Phenotype | Genes | Variants | Alleles | ID dbSNP/HGMD Accession | Annotation | InterVar/CADD score | α-LELY (Y/N) |
Family history/evaluation |
|---|---|---|---|---|---|---|---|---|---|---|
| 23 | HS | Moderately Severe | SPTB (exon 3) | NM_000347:c.C361T (p.Q121*) | HT | New | Nonsense | Pathogenic/NA | Y | Mother with mild HS. Parental sample not available |
| 28 | HS | Mild | SPTB (exon 3) | NM_000347:c.T458A (p.I153N) | HT | New | Missense | Unc Sig/29.8 | Y | Two children with HS. Parental sample not available |
| 26 | HS | Mild | SPTB (exon 3) | NM_000347:c.397_398del (p.M133fs) | HT | New | Frameshift deletion | Pathogenic/NA | N | NA/ Parental sample not available |
| 13 | HS | NA | SPTB (exon 7) | NM_000347:c.792delA (p.K264fs) | HT | New | Frameshift deletion | Pathogenic/NA | Y | Confirmed mutation in 2 sons with mild HS |
| 7 | HS | Moderately Severe | SPTB (exon 9) | NM_000347:c.1137_1138del (p.K379fs) | HT | New | Frameshift deletion | Pathogenic/NA | Y | No family history. Confirmed de novo mutation |
| 21 | HS | Moderate | SPTB (exon 13) | NM_000347:c.C2659T (p.Q887*) | HT | New | Nonsense | Pathogenic | Y | Son with HS. Parental sample not available |
| 6 | HS | Mild | SPTB (intron 19/20) | NM_000347:c.4267-1G > A | HT | New | Splice site | Unc Sig/NA | Y | Confirmed mutation in 2 daughters with mild HS |
| 2 | HS | Mild | SPTB (intron 19/20) | NM_000347:c.4266 + 1G > T | HT | New | Splice site | Unc Sig/NA | Y | Confirmed mutation in father with mild HS |
| 5 | HS | Moderate | SPTB (exon 20) | NM_000347:c.A4414T (p.K1472*) | HT | New | Nonsense | Pathogenic/NA | Y | Son with HS. Confirmed de novo mutation |
| 35 | HS | Mild | SPTA1 (exon 13) | NM_003126:c.1629delT (p.I543fs) | HT | New | Frameshift deletion | Pathogenic/NA |
Y (trans) |
Confirmed frameshift mutation in daughter and brother with mild HS |
| 24 | HS | Mild | SPTA1 (exon 17) | NM_003126:c.2239delA (p.T747fs) | HT | New | Frameshift deletion | Pathogenic/NA |
Y (trans) |
Confirmed frameshift mutation in daughter with iron deficit |
| 18 | HS | Mild | SPTA1 (exon 29) | NM_003126:c.4110delT (p.L1370fs) | HT | New | Frameshift deletion | Pathogenic/NA |
Y (cis) |
Confirmed mutation in one affected brother with mild HS. Both with α-LELY |
| 27 | HS | Mild | SPTA1 (exon 30) | NM_003126:c.C4201T (p.Q1401*) | HT | rs866240607/ NA | Nonsense | Pathogenic/NA |
Y (cis) |
Confirmed mutation and α-LELY in affected father with mild HS |
| 46 | HS | Mild | ANK1 (exon 5) | NM_000037:c.G352A (p.A118T) | HT | New | Missense | Unc Sig/31 | N | Confirmed mutation in affected son with mild HS |
| 16 | HS | Moderate | ANK1 (exon 6) | NM_000037:c.C457T (p.Q153*) | HT | New | Nonsense | Pathogenic | Y | No Family history. Confirmed de novo mutation |
| 30 | HS | Mild | ANK1 (exon 6) | NM_000037:c.564_565insCACG (p.A189fs) | HT | New | Frameshift insertion | Likely pathog/NA | Y | Mother with iron deficiency. Parental sample not available |
| 1 | HS | Mild | ANK1 (exon 8) | NM_000037:c.T776C (p.L259P); | HT | New | Missense | Unc Sig/28.9 | Y (HO) | Corfirmed mutation in mother with HS |
| 8 | HS | Mild | ANK1 (intron 23/24) | NM_000037:c.2559-1G > A | HT | New | Splice site | Unc Sig/NA | Y | Confirmed mutation in two affected family members |
| 33 | HS | Moderately severe | ANK1 (exon 33) | NM_000037:c.4057_4058insCC (p.Q1353fs) | HT | New | Frameshift insertion | Likely pathog/NA | N | Corfirmed mutation in father with HS |
| 22 | HS | Mild | SLC4A1 (exon 13) | NM_000342:c.G1469A (p.R490H) | HT | CM994551/NA | Missense | Unc Sig/26.2 | Y | Son with HS. Parental sample not available |
| 31 | HS | Mild | SLC4A1 (exon 17) | NM_000342:c.C2278T (p.R760W) | HT |
rs37391682/ CM951170 |
Missense | Unc Sig/25.6 | N | Confirmed mutation in father with mild HS |
HS hereditary spherocytosis, HO homozygosis, HT heterozygosis, NA not available, Unc Sig uncertain significance, Y yes, N no