Long-read sequencing identifies a common transposition haplotype predisposing for CLCNKB deletions

Tschernoster, Nikolai; Erger, Florian; Kohl, Stefan; Reusch, Björn; Wenzel, Andrea; Walsh, Stephen; Thiele, Holger; Becker, Christian; Franitza, Marek; Bartram, Malte P.; Kömhoff, Martin; Schumacher, Lena; Kukat, Christian; Borodina, Tatiana; Quedenau, Claudia; Nürnberg, Peter; Rinschen, Markus M; Driller, Jan H.; Pedersen, Bjørn P.; Schlingmann, Karl P.; Hüttel, Bruno; Bockenhauer, Detlef; Beck, Bodo; Altmüller, Janine

doi:10.1186/s13073-023-01215-1

Table 1 Patient cohort

From: Long-read sequencing identifies a common transposition haplotype predisposing for CLCNKB deletions

Family patient ID	Sex	Age at study	Age at definite diagnosis	Country of origin	Phenotype	Other complications, remarks	eGFR (ml/min/1.73m²) or serum creatinine (mg/dl) on last follow up	Deletion alleles (letter code)
P1.1	Male	31	0	Syria; c	ABS	Destructive gouty arthritis	<15 (age 31 y)	C
P1.2	Male	22	0	Syria; c	ABS	Hyperuricemia	35 (age 22 y)	C
P1.3	Male	20	0	Syria; c	ABS	Hyperuricemia, seizures (normal EEG)	70 (age 19 y)	C
P2	Female	46	nd	UK-Asian	CBS	Short statue	27	E
P3	Female	18	1	UK-Asian	CBS	(polyhydramnios, but born 42 wks Presented with critical collapse with multisystem organ failure age 1 y in the context of enteroviral infection	70 (age 17 y)	E
P4	Male	15	7	UK-Asian	CBS	Childhood, initially presented age 2 y with growth failure, referred to nephrology age 7 y with persistent hypokalaemia	140 (age 8 y)	A
P5	Male	15	8	UK-black	GS	Childhood, presented age 7 y with abdominal pain and blood tests showed hypokalaemia/hypomagnesaemia	155 (age 10 y)	F
P6	Female	10	3	UK-Asian	CBS	Childhood, presented age 3 y with growth failure and noted to have hypokalaemia and alkalosis	180 (age 10 y)	H
P7	Female	32	~6	Italy	CBS, GS	Presented initially in Italy, notes only say that she presented initially as CBS, but then looked more and more like GS, so that BS3 was suspected.	102 (age 17 y)	B
P8	Male	18	2	Sri Lanka	ABS	Antenatal, (polyhydramnios, born at term), 3 siblings died in infancy of unclear cause in Sri Lanka	60 (age 17 y)	B
P9	Male	29	1	UK-black	ABS	Antenatal, (27 wk gestation), nephrocalcinosis, nephrotic range proteinuria (first noted age 13), quantified as 3.3 g/d	67 (age 16 y)	B, F
P10^a	Female	10	1	UK-white	nd	Born 34 wk (no polyhydramnios) presented age 4 days with weight loss, found to have HSD3B2 deficiency.	120 (age 1 y)	D
P11	Male	nd	1	Italy	ABS	Antenatal (polyhydramnios with 4 amnioreductions, born at term), intrauterine growth restriction, birthweight 2130g. In neonatal period noted to have hypoklaemic alkalosis	95 (age 3 y)	G
P12	Female	17	1	UK-Iranian	ABS	Antenatal (polyhydramnios, but born at term), presented at age 3 months with growth failure and severe electrolyte abnormalities: Na 120, K: 1.0)	50 (age 17 y)	E
P13	Male	29	7	Iran	CBS	Childhood, pre-school age presentation with growth failure, polyuria, hypokalaemia history of previous fetal loss with polyhydramnios	15 (creatinine 350, age 18 y)	E
P14	Female	3	1	UK-black	CBS	Presentation age 2 months with growth failure, noticed to have hypokalaemia	110 (age 3 y)	B, F
P15.1^b	Male	nd	nd	German, f	nd	5 wk	nd	A
P15.2^b	Male	nd	nd	German, f	nd	Childhood, age 4 years	nd	A
P16^b	Male	nd	nd	Turk, f	nd	5 wk	nd	nd
P17^{b, c}	Female	34	nd	Turk, c	ABS	Antenatal, (polyhydramnios, born at 28 wks gestation), polyuria, hypokalaemia, metabolic alkalosis, sensorineural deafness, digenic BS 4b	nd	B
P18	Female	29	22 mo	Congo, s	CBS	Childhood, pre-school age presentation with growth failure	90 (age 27 y)	F
P19	Female	27	2.5 mo	Turk, c	CBS	Infantile onset	Creatinine 1.3 (age 4.5 y)	nd
P20	Male	nd	nd	Turk, c	nd	nd	nd	B
P21	Male	23	3 wk	Turk, c	CBS	Antenatal (34 wk gestation) vomiting, hypokalaemic alkalosis	Creatinine 0.9 (age 14 y)	E
P22	Male	21	5 mo	Tamil	CBS	Infantile onset, vomiting, hypokalaemic alkalosis	Creatinine 0.3-0.4 (age 1 y)	nd
P23	Female	24	9 mo	France, s	CBS	Infantile onset, failure to thrive, polyuria	nd	F
P24	Female	20	5 wk	Arabia, c	CBS	Infantile onset	Creatinine 0.4 (age 2 mo)	E
P25	Female	32	nd	Rwanda, s	nd	nd	nd	nd
P26	Female	19	6 mo	Afghanistan, c	CBS	nd	nd	nd
P27	Male	18	2 mo	Turk, c	CBS	Failure to thrive	nd	E
P28	Female	16	nd	Turk, c	ABS	nd	nd	E
P29	Female	nd	nd	Turk, c	nd	nd	nd	E
P30	Male	nd	nd	Africa, s	CBS	nd	nd	B

ABS, antenatal BS; CBS, classical BS; GLS, Gitelmann-like syndrome; lower case letters in the country of origin column indicate c, consanguineous; familial (f); sporadic (s) case; wk, week; mo, months; y, years; nd, no data
^aPatient has been previously reported in Giri et al. [39]
^bPatients have been previously reported in Konrad et al. [17]
^cPatient has been previously reported in Schlingmann et al. [11]

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