Table 1.
Clinical and genetic information of cases carrying likely disease-causal variants.
| Family | Initial Dx | Final Dx | Clinical Features | Gene | Allele 1 | Allele 2 | Other alterations | Methods | Segregation |
|---|---|---|---|---|---|---|---|---|---|
| Ciliopathies | |||||||||
| RP-1232 | Alström | Alström | RP, hearing loss, obesity, diabetes, NPHP, hypogonadism, hypothyroidism, hyperinsulinemia, and acantosis nigricans | ALMS1 |
NM_015120.4:c.4252del;
p.(Arg1418Glyfs*55) |
NM_015120.4:c.4252del;
p.(Arg1418Glyfs*55) |
NGS | Y (AR) | |
| RP-2186 | Alström | Alström | Early RD, overweight, dilated cardiomyopathy, and diabetes | ALMS1 |
NM_015120.4:c.4477G>T; p.(Glu1493*)61 |
NM_015120.4: c.7571_7572del; p.(His2524Argfs*11)61 |
NGS | Y (AR) | |
| RP-2177 | Alström | Alström | CRD, hearing loss, and dilated cardiomyopathy | ALMS1 |
NM_015120.4:c.808C>T; p.(Arg270*)31 |
NM_015120.4:c.11618_11619del; p.(Ser3873Tyrfs*19)61 |
NGS | na | |
| RP-2069 | BBS | BBS | CRD, polydactyly, maturation and learning delay, obesity, and chronic renal failure | IFT27 |
NM_006860.4:c.104A>G; p.(Tyr35Cys) |
NM_006860.4:c.350-2A>G | NGS | na | |
| RP-2167 | BBS | BBS | CRD, obesity, polydactyly and brachydactyly, psychomotor and learning delay, and behaviour disorder | BBS2 |
NM_031885.2:c.471G>A; Affecting 5′ splicing site31 |
NM_031885.2:c.1237C>T; p.(Arg413*)30 | NGS | na | |
| RP-2228 | BBS | BBS | RP, ID, overweight since infancy, brachydactyly, chronic renal failure, and renal transplant | BBS1 |
NM_024649.4:c.1645G>T; p.(Glu549*)33 |
NM_024649.4:c.118del; p.(Cys40Alafs*2)62 |
MKKS NM_018848.3:c.724G>T; p.(Ala242Ser)32 | chip + NGS | Y* |
| RP-1814 | Joubert | Joubert | RD, nystagmus, psychomotor delay, cerebellar atrophy, chronic renal failure, and macrocephaly | CEP290 |
NM_025114.3:c.4028del; p.(Lys1343Argfs*2)34 |
NM_025114.3:c.7341dup; p.(Leu2448Thrfs*8)35 |
chip + NGS | Y (AR) | |
| Other specific syndromes | |||||||||
| RP-1724 | ZSSD | ZSSD | Early RP, congenital deafness, neonatal jaundice, intrahepatic biliary dysgenesis, encephalopathy, ID, hiperprolactinemia, and gynecomastia | PEX1 |
NM_000466.2:c.2528G>A; p.(Gly843Asp)36 |
NM_000466.2:c.2528G>A; p.(Gly843Asp)36 |
NGS | NA | |
| V-0799 | Pseudoxanthoma elasticum | Pseudoxanthoma elasticum | Macular atrophy, angioid streaks, and neovascular membrane | ABCC6 |
NM_001171.5:c.1483_1485del;
p.(Leu495del) |
NM_001171.5:c.1483_1485del;
p.(Leu495del) |
NGS | Y (AR) | |
| Miscellanea | |||||||||
| RP-0485 | RP + ID + deafness + congenital malformations | Usher + Koolen de Vries | RP, mild ID, hearing loss, ASD, macrocephaly, and low-set ears | USH2A | NM_206933.2:c.1876C>T; p.(Arg626*)43 | NM_206933.2:c.13010C>T; p.(Thr4337Met)44 | 721Kb monosomy at 17q21.31† | NGS + aCGH | Y (USH2A: AR CNV: de novo) |
| RP-1430 | RP + ID | Cohen | RP and ID | VPS13B | NM_017890.4:c.1512del; p.(Glu505Lysfs*23) | NM_017890.4:c.1512del; p.(Glu505Lysfs*23) | NGS | Y* | |
| RP-1613 | RP + neuroendocrine alteration | OTX2-related | LCA, congenital nystagmus, psychomotor delay, compulsive eating, muscular hypotonia, obesity, and hypogonadism | OTX2 | NM_172337.2:c.255 G > A; p.(Trp85*) | NGS | Y (de novo) | ||
| RP-2140 | RP + neuroendocrine alteration | OTX2-related | Congenital nystagmus, early-onset CRD, developmental delay, and panhypopituitarism | OTX2 |
NM_172337.2:c.559
C
>
T;
p.(Gln187*) |
NGS | Y (de novo) | ||
| RP-2273 | RP + neuroendocrine alteration | BBS | Congenital nystagmus, LCA, developmental delay, congenital hypothalamic obesity, hypogonadism, acantosis nigricans, and clinodactyly | CEP41 |
NM_018718.2:c.5
C
>
T;
p.(Ser2Phe) |
NM_018718.2:c.5 C > T; p.(Ser2Phe) | NGS | na | |
Novel likely pathogenic variants found in this study are represented in bold. *Segregation of families RP-2228 and RP-1430 could be only done in an unaffected sister and father, respectively. †Monosomy at 17q21.3 (arr[GRCh37] 17q21.31(43417434_44138572)x1) encompassed the following genes: ARHGAP27, PLEKHM1, MIR4315-1, MIR4315-2, LRRC37A4, LOC101929001, DND1P1, LOC644172, RPS26P8, CRHR1, MGC57346, SPPL2C, MAPT, MAPT-IT1, STH, KANSL1. Abbreviations: aCGH: array–based comparative genomic hybridization; AR: autosomal recessive; ASD: atrial septal defect; BBS: Bardet-Biedl syndrome; CRD: cone-rod dystrophy; Dx: diagnosis; ID: intellectual disability; LCA: Leber congenital amaurosis; na: not available; NGS: next-generation sequencing; NPHP: nephronophthisis; RD: retinal dystrophy; RP: retinitis pigmentosa; Y: yes; ZSSD: Zellweger syndrome spectrum disorder.