Table 1. Patients included in the study with type of mutation, biochemical features of the mutated protein and main clinical features.

Patient	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19
Age in years at onset of study	29	10	13	15	4	2 (deceased)	18	17	6	16	14	4	20	3	33	28	44	21	20
Origin	Italy (Sardinia)	Italy (Sardinia)	Italy (Sardinia)	Italy (Sardinia)	Italy (Sardinia)	Turkey	Turkey	Turkey	Turkey	Libya	Libya	Libya	Spain	Italy	Norway	Norway	Canada	Israel	Israel
Original classification	CS	CS	CS	CS	CS	CS	CS	CS	CS	CS	CS	CS	CS	CS	CISS1	CISS1	CISS1	CISS1	CISS1
Mutation number	M1 M2	M2	M2	M1 M2	M1	M3	M3	M3	M4	M7	M7	M7	M5 M6	M8	M11	M11	M9 M10	M12 M13	M12 M13
Type of mutation	Mis Fs	Fs	Fs	Mis Fs	Mis	Fs	Fs	Fs	Nons	Ins	Ins	Ins	Fs Ins	Mis	Fs	Fs	Nons Mis	Mis Mis	Mis Mis
CRLF1-secretion at 48 h (%)a	6 6	6	6	6 6	6	10	10	10	37	0	0	0	0 0	0	28	28	0 63	42 74	42 74
Phenotypic severity	Severe	Severe	Severe	Severe	Severe	Severe	Severe	Severe	Severe	Severe	Severe	Severe	Severe	Severe	Severe	Intermediate	Intermediate	Mild	Mild
Hyperthermia	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	−	n.a.	n.a.	n.a.
Contraction of oropharyngeal muscles	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	−	n.a.	n.a.	n.a.
Dehydration	−	−	−	−	+	+	−	−	n.a.	−	+	−	−	−	−	−	n.a.	n.a.	n.a.
Cyanosis	+	+	+	+	+	−	−	−	+	+	+	+	−	−	−	−	n.a.	n.a.	n.a.
Swallowing/feeding difficulties	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	n.a.	n.a.
Nasogastric feeding	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	n.a.	n.a.	n.a.
Camptodactyly	+	+	+	+	+	+	+	+	+	−	−	−	+	+	+	+	+	n.a.	n.a.
Chubby cheeks	+	+	+	+	+	+	−	−	+	−	−	−	−	−	+	−	n.a.	n.a.	n.a.
Foot anomalies	−	−	+	−	−	+	+	+	n.a.	−	−	+	−	+	−	+	+	+	+
High arched palate	+	n.a.	−	−	−	+	+	−	n.a.	+	+	+	+	+	+	+	+	n.a.	n.a.
Depressed nasal bridge	+	+	+	−	−	n.a.	+	+	n.a	−	−	−	−	−	−	−	n.a.	+	+
Cold induced sweating (cut off 6 years)	+	+	+	+			+	+	n.a.	+	+	+	+		+	+	+	+	+
Scoliosis (cut off 2 years)	+	+	+	+	+		+	+	n.a.	+	+	+	+	+	+	+	+	+	+
Joint contractures	+	+	n.a.	n.a.	−	+	+	+	n.a.	−	−	+	+	−	+	+	+	+	+
Psychomotor retardation	+	+	+	+	−	+	+	+	n.a.	−	−	−	−	−	−	−	−	−	−

Abbreviations: Fs, frameshift; Mis, missense; Nons, nonsense; n.a., not available.

^aCRLF1 secretion level of mutant forms compared with wild type.