Table 1:
Clinical summary of Hatipoğlu syndrome caused by biallelic DPP9 Loss-of-Function mutations
| Clinical synopsis and genetics | HPO Terms | Family 1 | Family 2 | Family 3 | Present in all cases | ||
|---|---|---|---|---|---|---|---|
| Country of origin | USA (Ashkenazi) | Turkey | Israel (Bedouin) | ||||
| Propositus number (refer to pedigrees) | II:2 | II:4 | II:11 | III:1 | |||
| Sex, (year of birth) | Male (2017) | Male (2008) | Male (2011) | Male (2012) | |||
| IUGR, (birth weight in kg) | HP:0001511 | + (2.3) | − (3.6) | − (3.2) | + (2.1) | ||
| Gene | DPP9 | DPP9 | DPP9 | NLRP1 | |||
| Inheritance | HP:0000007 | cpd htz | hmz | hmz | hmz | ✔ | htz |
| cDNA change (NM_139159) | maternal:c.641C>G | c.2551C>T | c.331C>T | ||||
| paternal:c.499G>A | |||||||
| Expected protein change (Q86TI2–2) | maternal: p.S214* | p.Q851* | p.R111* | p.P1214R | |||
| paternal: p.G167S | |||||||
| Observed protein change (Q86TI2–2) | maternal: p.0 | p.0 | n.d. | ||||
| paternal: p.G167S | |||||||
| Immune defects | |||||||
| Infantile eczema | HP:0000964 | + (after BM transplantation) | + | − | − | ||
| Recurrent fevers | HP:0032323 | + | bimonthly | + | + | ✔ | ✔ |
| Asthma | HP:0002099 | − | + | − | + | ||
| Repeated infections | HP:0002719 | + | + | + | + | ✔ | ✔ |
| Herpes infections | HP:0005353 | + | + (facial) | + | + | ✔ | |
| Bronchitis | HP:0012387 | + | + | − | + | ||
| Prone to acute otitis media | HP:0000403 | + | + | + | − | ||
| Pancytopenia | HP:0001876 | + | + | + | + | ✔ | |
| Anemia | HP:0001903 | + | + | + | + | ✔ | ✔ |
| Selective immunodeficiency | HP:0002721 | + | + | n.d. | n.d. | ||
| Severe allergies | HP:0012393 | + (sesame) | + | − | − | ||
| Behavioural/Neurological traits | |||||||
| Learning Disability | HP:0001328 | + | + | − | + | ||
| Speech delay | HP:0000750 | + | + | − | + | ||
| Slurred speech | HP:0001350 | + | + | − | − | ||
| Autism spectrum disorder | HP:0000729 | + | − | − | + | ||
| Skin findings and its appendages | |||||||
| Thick skin | HP:0001072 | + | − | − | − | ||
| Anhidrosis | HP:0000970 | − | + | − | − | ||
| Dry skin | HP:0000958 | − | + | − | − | ||
| Atopic dermatitis | HP:0001047 | + | + | − | − | ||
| Petechiae | HP:0000967 | + | + | + | + | ✔ | |
| Fair hair | HP:0002286 | + | + | − | − | ||
| Premature hair graying | HP:0002216 | − | + | − | − | ||
| Hypo- and hyper-pigmented macules | HP:0007441 | + | + | + | − | ||
| Delayed wound healing | HP:0001058 | − | + | − | − | ||
| Craniofacial dysmorphisms | |||||||
| Downslanted palpebral fissures | HP:0000494 | + | + | − | − | ||
| Broad forehead | HP:0002373 | + | − | − | − | ||
| Bone / skeletal abnormalities | |||||||
| Hemivertebrae | HP:0002937 | n.d. | n.d. | + | + | ||
| Other clinical manifestations | |||||||
| Proportionate short stature | HP:0003508 | + | + | + (−2.1 SD) | + (−1.8 SD) | ✔ | ✔ |
| Failure to thrive | HP:0001508 | + | + | + | + | ✔ | ✔ |
| Febrile seizures | HP:0002373 | + | − | − | − | ||
| Cryptorchidism / hypospadias | HP:0000028 | + | − | − | − | ||
| Inguinal hernia | HP:0000776 | + | − | − | + | ||
| Poor feeding | HP:0011968 | + | + | − | − | ||
n.d., not determined; +, affirmative; −, negative; BM, bone marrow; cpd, compound: hmz, homozygous; htz, heterozygous