Table 2 Clinical features of patients with NBAS deficiency reported in previous studies
Patient ID | Sex | Nationality | Genotype | Onset age of ALF or LC (Year) | Age at last visit (Year) | Number of ALF | Number of LC | ALF or LC Fever depended | Skeletal system and musculature | Typical morphological characteristics | Integument (Cutis laxa) | Nervous system | Immune system | Pelger Huët anomaly | Other clinical manifestations |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | F | Germany | c.[558_560del];[686dup] p.[Ile187del];[Ser230Glnfs*4] | 1.8 | 18 | 2 | 12 | YES | Short stature (− 2.67SD) | NA | NA | Optic atrophy | NO | NO | Hypotelorism |
2 | F | Germany | c.[2708 T > G];[2708 T > G] p.[Leu903Arg];[Leu903Arg] | 0.6 | 22 | 7 | 6 | YES | Short stature (−2.08SD) | NA | NA | Epilepsy; Learning disability (IQ 77) | NO | NO | Acute renal failure; Hypotelorism |
3 | F | Germany | c.[603_605del];[3164 T > C] p.[Leu202del];[Leu1055Pro] | 0.8 | 18 | 5 | 8 | YES | Short stature (−4.24SD) | NA | NA | NO | NO | NO | Hypotelorism; disease |
4 | F | Germany | c.[2708 T > G];[2827G > T] p.[Leu903Arg];[Glu943*] | 0.7 | 37 | NA | NA | YES | Short stature (−2.25SD) | NA | NA | Coordination deficit Intellectual disability (IQ 50) | NO | NO | Hypotelorism |
5 | M | Germany | c.[3010C > T];[3164 T > C] p.[Arg1004*];[Leu1055Pro] | 0.6 | 14 | 10 | 4 | YES | NO | NA | NA | NO | NO | NO | Hypotelorism; Cardiomyopathy |
6 | M | Great Britain | c.[1533_1545del];[2951 T > G] p.[Ile512Thrfs*4];[Ile984Ser] | 1.5 | 3 | 5 | 2 | YES | Short stature (−2.91SD) | NA | NA | Motor delay | NO | NA | NO |
7 | F | Croatia | c.[1042C > T];[2203_3C > G] p.[Pro348Ser];[?] | 0.9 | 9 | 4 | 5 | YES | NO | NA | NA | NO | NO | NA | Hypotelorism |
8 | F | Croatia | c.[1042C > T];[2203_3C > G] p.[Pro348Ser];[?] | 6.7 | 11 | 1 | 2 | YES | Short stature (−2.71SD) | NA | NA | NO | NO | YES | Erythema nodosum; Crohn’s disease |
9 | M | Germany/ Turkey | c.[1187G > A];[2330C > A] p.[Trp396*];[Pro777His] | 1.8 | 8 | 1 | 3 | YES | NO | NA | NA | NO | NO | NA | NO |
10 | F | United States | c.[118-2A > G];[2524G > T] p.[?];[Val842Phe] | 1.5 | 4 | 3 | NA | YES | Short stature (−2.62SD) | NA | NA | NO | NO | NA | Episodes of mild hypoglycemia during acute illness |
11 | F | United States | c.[686dup];[3164 T > C]p.[Ser230Glnfs*4];[Leu1055Pro] | 0.3 | 18 | 5 | 2 | YES | Short stature (−2.35SD) | NA | NA | NO | NO | NA | NO |
12 | M | France | c.[2827G > T];[exons39–40del] p.[Glu943*];[Val2145_Glu2237del] | 0.6 | 1.8 | 8 | 0 | YES | Short stature (−2.48SD); Skeletal dysplasia; Mild hypotonia; | NA | NA | Optic atrophy; Left hemi-paresis; Motor delay; Epilepsy; Hypotonia; | Hypogammaglobulinemia | Yes | Lymphopenia during crisis; Neuroblastoma |
13 | M | Germany | c.[1278A > C];[exons49–50del] p.[Cys426Trp]; [Val1528Glyfs*2] | 0.8 | 8 | 1 | 3 | YES | Short stature (−2.07SD) | NA | NA | NO | Hypogammaglobulinemia | YES | NO |
14 | F | Germany | c.[173-2A > G];[3363A > G] p.[=];[Ile1121Met] | 2 | 16 | 12 | 1 | YES | NO | NA | NA | NO | NA | NA | NO |
15 | F | American | c.[409C > T];[1186 T > A] p.[Arg137Trp];[Trp396Arg] | 1.9 | 5 | 3 | NA | YES | Short stature (−3.5SD); Skeletal dysplasia; Cervical instability; Fractures (1 skull and 1 left femur fracture); | YES | YES | Motor delay | Reduced natural killer cells | YES | NO |
16 | M | Switzerland | c.[284C > T];[850A > T] p.[Ala95Val];[Lys284Ter] | 0.4 | 12 | 0 | >1 | YES | Short stature (−3SD); Skeletal dysplasia; Cervical instability; | YES | YES | Optic atrophy | Hypogammaglobulinemia; Reduced natural killer cells | YES | NO |
17 | F | NA | c.[2819A > C] p.[His940Pro] | 0.3 | 4 | ≥1 | ≥1 | YES | Short stature | NO | NO | NO | NO | NA | NO |
18 | M | Japanese | c.[1018G > C];[2674 G > T] p.[Gly340Arg]; [Val892Phe] | 3.3 | 3.5 | 2 | 0 | YES | Short stature | NO | NA | NO | NO | YES | Renal failure; |
19 | F | China | c.[1840delG]; [3596G > A] p.[Ala614Leufs*3]; [Cys1199Tyr] | 0.5 | 0.58 | 1 | 2 | YES | NO | YES | NO | NO | NA | NA | NO |
20 | M | China | c.[6751_6754delCTCC]; [3596-G > A] p.[Leu2251Cysfs*5]; [Cys 1199Tyr] | 1.2 | 5.4 | ≥2 | ≥3 | YES | NO | NA | NA | NO | Reduced natural killer cells | YES | NO |
21 | M | China | c.[7041_7043delTCT];[3759delC] p.[2347_2348delLLinsL];[Thr1254Hisfs*16] | NA | 0.75 | NA | ≥2 | YES | NO | YES | NA | NO | NO | YES | NO |
22 | F | China | c.[3596G > A];[209 + 1G > A] p.[Cys1199Tyr];[?] | NA | 4 | NA | ≥1 | YES | NO | NO | NO | NO | NA | NA | NO |
23 | M | China | c.[6611_6612insCA];[3596G > A] p.[Met2204Ifs*3];[Cys1199Tyr] | 0.5 | 6 .9 | 5 | 3 | YES | Short stature (−1.42SD) | NO | NO | NA | NA | NA | NO |
24 | M | China | c.[3596G > A];[586C > T] p.[Cys1199Tyr];[Gln196X] | 0.6 | 4.7 | 1 | 2 | YES | Short stature(−1.47SD) | NO | NO | NA | NA | NA | NO |
25 | M | China | c.[5389 + 1G > T];[2407G > A] p[?];[Glu803Lys] | 0.5 | 2.3 | 10 | 1 | YES | NO | NO | NO | NA | NA | NA | NO |
26 | F | NA | c.[2827G > T];[5741G > A] p.[Glu943*];[Arg1914His] | 0.7 | 4.9 | NA | ≥2 | YES | Short stature(−6SD); Skeletal dysplasia; Delayed bone maturation; Hypotonia | YES | NA | Optic atrophy; Motor delay; Speech delay | Reduced B cells; Initially neutropenia; Hypogammaglobulinemia | YES | NO |
27 | F | Portuguese | c.[680A > C];[1749G > A] p.[His227Pro];[Trp583*.] | 2.8 | 3.9 | 0 | 2 | YES | Short stature; Poor muscular development; Slightly delayed bone age (18 months at 23 months of age); | YES | NO | NO | NO | NA | NO |
28 | F | Portuguese | c.[680A > C];[1749G > A] p.[His227Pro];[Trp583*.] | 1.5 | 9 | 2 | >30 | YES | Short stature; Low bone mineral density | NO | NO | NO | NO | NA | NO |
29 | NA | NA | c.[284C > T]; [2802G > A] p.[Ala95Val; [Trp934*] | NA | NA | ≥1 | NA | NA | Short stature; Cervical instability; Reduced bone mineral density; Muscular hypotrophy | NA | YES | Motor delay | Hypogammaglobulinemia | NO | High pitched voice |
30 | NA | NA | c.[812 T > C]; [812 T > C] p.[Leu271Pro]; [Leu271Pro] | NA | NA | ≥1 | NA | NA | Short stature; Muscular hypotonia and hypotrophy | NA | NO | Motor delay | Hypogammaglobulinemia | NO | Protuberant abdomen; High pitched voice |
31 | NA | NA | c.[1241C > T];[2950delA; p.[Ser414Phe];[Ile984Leufs*8] | 0.2 | NA | ≥1 | NA | NA | Short stature; Skeletal dysplasia; Reduced bone mineral density; Pathologic fracture; Muscular hypotonia and hypotrophy | NA | YES | Optic atrophy | Hypogammaglobulinemia | YES | Insulin dependent diabetes mellitus; Chronic lung disease; High pitched voice |
32 | NA | NA | c.[1241C > T];([6236 + 1_6237–1]_[6432+ 1_6433–1] del); p.[Ser414Phe]; [Glu2080*] | 0.7 | NA | 0 | ≥1 | NA | Short stature; Skeletal dysplasia; Reduced bone mineral density; Muscular hypotonia and hypotrophy | NA | YES | Optic atrophy; Motor delay | NO | YES | Relative macrocephal; Decreased serum IGF1 and IGFBP3; High pitched voice |
33 | NA | NA | c.[1549C > T];[5041_5048del]; p.[Arg517Cys];[Ser1681Glnfs*37] | 0.7 | NA | ≥1 | NA | NA | Reduced bone mineral density; Skeletal dysplasia; Scoliosis; Pathologic fracture; Muscular hypotonia and hypotrophy | NA | NO | NO | Hypogammaglobulinemia | NO | Cataract and dislocation of the lens; Nephrolithiasis; High pitched voice |
34 | NA | NA | c.[1550G > A]; [6805G > T]; p.[Arg517His]; [Glu2269*] | 3.0 | NA | ≥1 | NA | NA | NO | NA | NO | NO | NO | NO | NO |
35 | NA | NA | c.[1550G > A]; [6805G > T]; p.[Arg517His]; [Glu2269*] | NA | NA | ≥1 | NA | NA | NO | NO | NO | NO | NO | NO | Preemptive family testing |
36 | NA | NA | c.[2191A > C]; [2191A > C]; p.[Thr731Pro]; [Thr731Pro] | 1 | NA | ≥1 | NA | NA | Short stature | NO | NO | NO | NO | NO | Liver transplantation |
37 | NA | NA | c.[2330C > A]; [2330C > A]; p.[Pro777His]; [Pro777His] | 2.7 | NA | ≥1 | NA | NA | NO | NO | NO | NO | NO | NO | Elevated 3-methylglutaconic in urine; Vitamin D deficiency |
38 | NA | NA | c.[2330C > A]; [2330C > A]; p.[Pro777His]; [Pro777His] | 3.2 | NA | ≥1 | NA | NA | NO | NO | NO | NO | NO | NO | Vitamin D deficiency |
39 | NA | NA | c.[2809C > G]; ([5138 + 1_5139–1]_7116del) p.[Pro937Ala]; [?] | 0.7 | NA | ≥1 | NA | NA | Short stature | NO | NO | NO | NO | NO | NO |
40 | NA | NA | c.[2819A > C];[2819A > C]; p.[His940Pro];[His940Pro] | 0.2 | NA | ≥1 | NA | NA | NO | NO | NO | NO | Reduced NK cells | NO | NO |
41 | NA | NA | c.[2951 T > G]; [2827G > T]; p.(Ile984Ser); (Glu943*) | 2.6 | NA | ≥1 | NA | NA | Short stature; Skeletal dysplasia; Delayed skeletal maturation | NO | NO | NO | NO | YES | Precocious puberty; High pitched voice |
42 | NA | NA | c.[3164 T > C]; ([5027 + 1_5028–1] _[5724 + 1_5725–1] del); p.[Leu1055Pro]; [Glu1676Aspfs*10] | 1.3 | NA | ≥1 | NA | NA | NO | NO | NO | NO | Hypogammaglobulinemia | NO | NO |
43 | NA | NA | c.[3363A > G]; [513 + 2 T > C]; p.[Ile1121Met]; [?] | 1.0 | NA | 0 | ≥1 | NA | Short stature | NO | NO | NO | Hypogammaglobulinemia | NO | NO |
44 | NA | NA | c.[3386C > T]; [3386C > T]; p.[Ser1129Phe]; [Ser1129Phe] | 2.3 | NA | ≥1 | NA | NA | NO | NO | NO | NO | NO | NO | Elevated 3-methylglutaconic and 3-methylglutaric in urine |
45 | NA | NA | c.[3386C > T]; [3386C > T]; p.[Ser1129Phe]; [Ser1129Phe] | 1.8 | NA | ≥1 | NA | NA | NO | NO | NO | NO | NO | NO | Elevated 3- methylglutaconic and 3-methylglutaric in urine |
46 | NA | NA | c.[3534C > A];[1342-6A > G]; p.[Ser1178Arg];[?] | 0.8 | NA | ≥1 | NA | NA | NO | NO | NO | NO | Hypogammaglobulinemia Reduced NK cells | NO | During crisis: seizures, cholecystitis, truncal exanthema, hypophosphatemia, anemia, lymphopenia, decrease of neutrophils |
47 | NA | NA | c.[3602A > C]; [3602A > C]; p.[Gln1201Pro]; [Gln1201Pro] | 0.8 | NA | ≥1 | NA | NA | NO | NO | NO | NO | NO | NO | Liver transplantation |
48 | NA | NA | c.[5741G > A];[1528C > T]; p.[Arg1914His];[Arg510*] | NA | NA | 0 | ≥1 | NA | Short stature; Delayed skeletal maturation; Skeletal dysplasia; Muscular hypotonia and hypotrophy | NA | YES | Motor delay; Intellectual disability | Hypogammaglobulinemia | NO | NO |
49 | NA | NA | c.[5740C > G];[6877delC]; p.[Arg1914Gly]; [Leu2293Cysfs*9] | 0.5 | NA | ≥1 | NA | NA | Short stature; Reduced bone mineral density; Delayed skeletal maturation; Skeletal dysplasia; Muscular hypotonia and hypotrophy | NA | YES | Motor delay; Optic atrophy | Hypogammaglobulinemia | YES | High pitched voice |
50 | NA | NA | c.[5761G > C]; [686dupT]; p.[Ala1921Pro]; [Ser230Glnfs*4] | 0.4 | NA | 0 | ≥1 | NA | NA | NA | NO | NO | Hypogammaglobulinemia | YES | NO |
51 | NA | NA | c.[6840G > T]; [6840G > T] p.[?];[?] | 0.3 | NA | 0 | ≥1 | NA | Short stature; Skeletal dysplasia; Delayed skeletal maturation | NA | NO | Optic atrophy; Motor delay | Hypogammaglobulinemia | YES | Rotary nystagmus; High pitched voice |
52 | NA | NA | c.[6966_6969delinsTC];[5547delC] p.[Gln2322Hisfs*18]; [Trp1850Glyfs*32] | 4.5 | NA | 0 | ≥1 | NA | NO | NA | NO | Optic atrophy; Motor delay | Hypogammaglobulinemia; Reduced NK cells | NO | Premature birth; Recurrent bacterial pneumonia |
53 | NA | NA | c.[767G > A];[2012 T > G]; p.[Cys256Tyr]; [Phe671Cys] | 0.1 | NA | 0 | ≥1 | NA | Short stature | NA | NA | Intellectual disability; Motor delay | NO | NO | NO |
54 | NA | NA | c.[2535G > T]; [5761G > C] p.[Trp845Cys]; [Ala1921Pro] | NA | NA | ≥1 | NA | NA | Short stature | NA | NA | NO | NA | NO | NO |
55 | M | Italy | c.[6840G > A];[686dupT] p.[Gly2238_Thr2280del];[Ser230fsGln*4] | NA | 7 | 0 | ≥1 | NA | Short stature; Skeletal dysplasia Reduced bone mineral density; | YES | NA | Neurodevelopmental delay with normal intelligence | Hypogammaglobulinemia | YES | Coeliac disease; Congenital bilateral glaucoma; Primary hypothyroidism |
56 | F | Italy | c.[6840G > A];[1501C > T] p.[Gly2238_Thr2280del];[Arg501*] | NA | 4 | 0 | ≥1 | NA | Short stature; Skeletal dysplasia | YES | NA | Neurodevelopmental delay with normal intelligence | Hypogammaglobulinemia | YES | Premature birth; Retinopathy of prematurity |