Table 1 Previous reports on FLNA gene variants associated with severe lung disorders

Gerard-Blanluet et al., 2006 [19]

Male twins*

Missense mutation c.7922C > T (p.Pro2641Leu)

Severe bronchopulmonary dysplasia (BPD)

Not provided

26

26 weeks

None

Yes

Death of 1 infant at 8 mo; Follow-up until age 6 years (intercurrent respiratory infection)

*same family

Female*

Missense mutation c.7922C > T (p.Pro2641Leu)

Severe BPD

Not provided

24

24 weeks

None

Yes

Follow-up until age 2.5 years

De Wit et al., 2011 [9]

Female

Missense mutation c.220G > A (p.Gly74Arg)

Lobar emphysema (right middle lobe); bronchomalacia of right bronchial tree; frequent respiratory infections.

Severe lobar emphysema of right middle lobe; displacement of mediastinal structures

term

3 months

Lobectomy (right middle lobe)

Yes

Weaned from oxygen at 1 year, 7 months

Masurel-Paulet et al. 2011 [2]

Male

Mosaic nonsense mutation c.994delG (p.Lys331*)

Progression to severe lung disease

Congenital lobar emphysema;

term

3 months

Subtotal left upper lobectomy

Yes

Age 6 years. Supplemental oxygen during sleep

Clapham et al., 2012 [21]

Female

3′ FLNA deletion sparing first exon

Pulmonary emphysema involving multiple lobes

Not provided

39

2 months

None

Yes

Death at 7 months

Female

3′ FLNA deletion and 5’FLNA duplication

Apical bullae of lung

Not provided

Not provided

ND

ND

Yes

Not provided

Female

Deletion entire FLNA gene

Lobar emphysema

Not provided

Not provided

ND

ND

Yes

Not provided

Reinstein et al., 2013 [22]

Female (case F3)

Truncating mutation c.2193C > A (p.Tyr731*)

Pulmonary hypertension, focal hyperinflation with minimal patchy atelectasis

Not provided

Not provided

6 years

ND

Yes

Not provided

Lord et al., 2014 [17]

Female

Truncating mutation c.5683G3 > T (p.Gly1895*)

Progression to severe lung disease

Cystic pulmonary lesions;

36

24 days

none

Yes

Weaned from oxygen at 22 months

Lange et al., 2015 [20]

Male (case 29)

Mosaic non sense mutation c.7055-7070delCTTTTGCAGTCAGCCT (p.Ser2352*)

Severe progressive obstructive lung disease

Not provided

ND

38 years

Consideration of lung transplantation

Yes

Not provided

Eltahir et al., 2016 [18]

Female

Duplication c.3153dupC (p.Val1052Argfs*17)

Progressive lung disease

Lower lobe airspace disease, hyperinflation (right middle and left upper lobes)

36

2 months

PDA ligation

Not performed

Death at 15 months

Shelmerdine et al., 2017 [13]

Female

Deletion c.88delG (p.Ala30Profs*28)

Progressive lung disease

Left upper lobe and lower inflation; coarse septal thickening

36 + 5

3 months

PDA ligation

Not performed

Died at 9 months

Female

Duplication c.6496dupA (p.lle2166Asnfs*3)

Multiple episodes of intercurrent pulmonary infections

Right upper and middle lobe over-inflation; coarse septal thickening; lower lobe atelectasis

term

7 months

Righ upper lobectomy, PDA ligation

Yes

Age 4 years

Female

Missense mutation c.1528G > A (p.Ala510Thr)

Meconium aspiration

Right upper and left upper lobe over-inflation; coarse septal thickening; Lower lobe atelectasis

40 + 4

At birth

None

Not performed

Age 3 years. Therapy with bronchodilatator

Female

Deletion c.2190_2193delTTAC (p.Tyr731Alafs*10)

Viral infections

Right upper and middle, left upper lobe over-inflation; Coarse septal thickening; Lower lobe atelectasis

38

3 months

None

Not performed

Age 6 years. Supplementary oxygen support

Burrage et al., 2017 [14]

Female

Duplication c.4596dupG (p.Ser1533Glufs*12)

Progressive lung disease

In all patients, severe pulmonary hyperinflation and hyperlucency with peripheral pulmonary vascular attenuation with parahilar and dependent lower lobe atelectasis and central pulmonary artery enlargement.

In all patient, pulmonary arterial hypertension was also diagnosed.

39

2–4 months

PDA ligation

Yes

Lung transplantation in all.

Five survivors at 19 months, 3 years, 4 years, 5.1 years, and 11.3 years respectively, post- follow-up. One died at 3 years

Female

Missense mutationc.5290G > A (p.Ala1764Thr)

Progressive lung disease

40

neonatal

PDA ligation

Yes

Female

Duplication c.4446_4447dupAT (p.Leu1483Tyrfs*19)

Progressive lung disease

38

neonatal

PDA ligation

Yes

Female

Duplication c.4617_4618delGC (p.Leu1540Alafs*4)

Progressive lung disease

34

neonatal

PDA ligation

Yes

Female

Duplication c.6585dupT (p.Pro2196Serfs*3)

Progressive lung disease

39

neonatal

PDA ligation

Yes

Female

Missense mutation c.2807A > G (p.Lys936Arg)

Progressive lung disease

38

neonatal

PDA ligation

Yes

Kinane et al. 2017 [15]

Female

Deletion c.6577delC (p.Arg2193Alafs*14)

Diffuse pulmonary abnormalities

Ground glass opacities, area of hyperacration, pulmonary hypertension

39

30 day

PDA ligation

Yes

Sasaki et al. 2018 [16]

Female

Deletion c.1709_1712del (p.Val570Alafs*105)

Progressive lung disease

Diffuse bilateral groung-glass opacification throughout the lung, interstitial thickening, cystic changes

37

1 month

None

Yes

Died at 4 months

Male

Splice site deletion c.6670-1delG

Several episodes of profound desaturation

Bilateral dependent and subsegmental atelectasis, scattered opacity, interstitial thickening

32

day of live 1

None

Yes

11 months, home oxigen

Our case

Male

Mosaic frameshift mutation c.7391_7403del; (p.Val2464Alafs*5)

Progressive lung disease

Lobar emphysema of the left upper lobe and a subsegmental atelectasis and areas of air trapping into the lower lobe

37

32 days

Left lobectomy

Tracheostomy

Yes

15 months

Mechanical ventilation