FIGURE 2.

Pathogenic variants in DNAAF6 located on the X chromosome were identified in four families. a) In family OP-1826/OP-1796 we found a 28 kb deletion (del) including the first exon of DNAAF6 and the first two exons of NUP62CL. b) In family OP-3577, a 10.6 kb deletion comprising DNAAF6 exons 2–4 was identified in OP-3577 I2. Segregation analyses revealed that neither her brother (OP-3577 I3) nor grandmother (OP-3577 02) carry the deletion, indicating that this is a de novo variant. OP-3577 I2 reported difficulties in getting pregnant and had one spontaneous abortion in the sixth week of pregnancy. c) In OP-3141 we identified a 400 kb deletion comprising DNAAF6, NUP62CL and RBM41. OP-3141 II1 is the fourth of six children. He has three older and one younger sister. The only brother died 10 days after birth owing to cardiorespiratory failure of unknown cause. His oldest sister gave birth to two male individuals: the first born died 3 months after birth, the second born died 4 months after birth. Both died of unknown causes with cardiorespiratory failure. With another partner, she gave birth to a healthy boy. The second oldest sister has three healthy children, two girls and a boy. The third oldest sister gave birth to a healthy boy. The younger sister has no children. d) In family OP-2835, a transition from G to A (c.266G>A) was identified in DNAAF6 exon 4, predicting premature stop of translation (p.Trp89*). Segregation analyses revealed that the mother (OP-2835 I2) and the grandmother (OP-2835 02) carry this variant in a heterozygous status whereas the father (OP-2835 I1) is unaffected. The great-grandmother of OP-2835 II1 had a spontaneous abortion (SAB) and gave birth to OP-2835 02, who inherited the DNAAF6 variant. The great-grandmother died owing to complications of an ectopic (ECT) pregnancy. OP-2835 02 gave birth to three daughters. The oldest one has two healthy children, a girl, who already has another healthy daughter, and a boy. The second oldest one, OP-2835 I2, is a carrier of the DNAAF6 variant and has two children. She had one ectopic pregnancy with a previous partner and with her current partner two spontaneous abortions and an ectopic pregnancy. OP-2835 II2 was her fourth pregnancy and is also a carrier of the DNAAF6 variant. In addition, she gave birth to the index primary ciliary dyskinesia (PCD) male individual OP-2835 II1, who was her sixth pregnancy and who carries the hemizygous DNAAF6 variant. The younger sister had one abortion and no children. PCD-affected males are shaded black and unaffected siblings are shaded white. Heterozygous female carriers are indicated by a central dot. Genotypes are indicated in the pedigrees.