The spondylometaphyseal dysplasias (SMDs) are a group of about a dozen rare disorders characterized by short stature, irregular, flat vertebrae, and metaphyseal abnormalities. Aside from spondylometaphyseal dysplasia Kozlowski type (MIM 184252) caused by mutations in TRPV4 (MIM 605427) and spondyloenchondrodysplasia (MIM 607944) resulting from mutations in ACP5 (MIM 171640), the genetic etiologies of SMDs are unknown. 1 Two of these unexplained SMDs have ophthalmologic manifestations: SMD with cone-rod dystrophy (SMD-CRD [MIM 608940]) and axial SMD with retinal degeneration (MIM 602271). Delineated clinically a decade ago, SMD-CRD is a presumed autosomal-recessive disorder with postnatal growth deficiency leading to profound short stature; rhizomelia with bowing of the lower extremities; platyspondyly with anterior vertebral protrusions; progressive metaphyseal irregularity and cupping with shortened tubular bones; and early-onset, progressive visual impairment associated with a pigmentary maculopathy and electroretinographic evidence of cone-rod dysfunction. 2–5 In contrast to retinitis pigmentosa, the CRDs have early involvement of cone photoreceptors. 6 Here, we report loss-of-function mutations in PCYT1A (MIM 123695) as the cause of SMD-CRD. PYCT1A encodes CTP: phosphocholine cytidylyltransferase (CCTa), 7, 8 a key enzyme in the CDP-choline or Kennedy pathway for de novo phosphatidylcholine biosynthesis. We used whole-exome and targeted sequencing of members of six unrelated families with eight individuals with SMD-CRD (Figure 1). Three families were submitted to the Baylor-Hopkins Center for Mendelian Genomics (BHCMG) through the online submission portal PhenoDB 9 and, to confirm our observations in the first three families, we recruited three additional families for targeted candidate gene sequencing. Local approval for this study was provided by the Johns Hopkins Institutional Review Board, and all participants signed an informed consent. The clinical features of these individuals are summarized in Table 1 and briefly reviewed here. Six of the subjects have been described in previous publications. 2, 5 Subject 1 (BH2265_1; family 1; Figure 2 A) was reported when she was 20 years old. 2 Now age 29, she has done well with continued linear growth to an adult height of 93.9 cm (À10. 7 SD) and modest progression of limitation of range of motion. Visual impairment has not progressed since around age 10. Subject 2 (BH2283_1; family 2, Figure 2 E), originally described at age 11 years, is now 20 years old with a current adult height of 139 cm (À5. 3 SD) and some progression of joint stiffening. His visual function declined during his second decade and he now requires low-vision aids. Subject 3 (BH2233_1; family 3) is a previously unreported 61-year-old female who was first seen at age 51. Although her skeletal phenotype is similar to that of the others described here, she had a late-onset retinal phenotype (Figure 2 B). Radiographs from childhood were reported to show platyspondyly and metaphyseal changes; adult radiographs show hypoplasia of the posterior vertebral bodies but no anterior vertebral protrusions. Adult height (measured at age 54) is 108.3 cm (À8. 4 SD). Visual symptoms were not apparent until middle age. An ERG at age 43 (performed because she had a brother with visual impairment) was said to be normal. By age