Table 1.

Brigham Genomic Medicine (BGM) genetic diagnoses to date

BGM no.	Gene	Inheritance	Diagnosis/novel or known syndrome, if known–phenotype exp.?	Prior genetic testing	Sequencing strategy	Solution strategy	Case source	Ref. or status
1	CHST11	AR	Skeletal malformation, malignant lymphoproliferative disease/novel	MA, K	Pbd WGS; S	CS	BWH, genetics	31
2	WISP3	AR (cons.)	Prog. pseudorheumatoid arthropathy, childhood (PPAC)/ OMIM 208230	Unknown	Pbd WGS; S	CS	BWH, Rheum	30
3	LOX	AD	Thoracic aortic aneurysm and dissection (TAAD)/novel	Panel	Pbd, c WGS; S	CC, MC, MO	BWH, Cardio	29
4	DOCK8	AR (cons.)	Infantile inflammatory bowel disease/novel	WES	Pbd WES re-anly	CC	BCH, GI	In prep.
5	C3	AD	Lower extremity ischemia/novel	None	Pbd, c WGS, S	CS, MC, FE	BWH, Rheum	In prep.
6	MVK	AR	Infantile-onset Crohn’s disease	None	Pbd, M WES	CC BCH, GI		In prep.
7	PIEZO2	AD (de novo)	Distal arthrogryposis type 5/gene discovery for OMIM 108145	None	Trio WGS	CC, MC, FE	BWH, genetics	23
8	TRPM4	AD	Right-sided structural heart defects and conduction defects	None	WES Pbd, c, M, F	CC	BCH, genetics	38
9	OBSCN/TTN a	AR	Nemaline myopathy	None	Trio WES	CC	BCH, genetics	38
10	TTN / GJB2 a	AR	Centronuclear myopathy and bilateral sensorineural hearing loss	None	Trio WES	CC	BCH, genetics	38
11	CTLA4	AD	Multisystem autoimmune disorder/novel	WES	WES s, M, 2F	CC	BWH, GI	39
12	CAPZB	AD (de novo)	Craniofacial anomalies and hypotonia/novel	K	Pbd WGS	CC, MO	FB/DGAP	40
13	RSPRY1	AR (cons.)	Progressive spondyloepimetaphyseal dysplasia and intel. disability/novel	None	Pbd WES	CC, MC, MO	FB/KFSH	41
14	MAP3K7	AD (de novo)	Global developmental delay and dysmorphic facies	WES	Trio WGS	CS, MC	FB/FCC	42, 43
15	F12	AD	Angioedema type 3/OMIM 610618	None	Pbd WGS	CC	BWH, Allergy & Imm.	42
16	POLR1A	AD (de novo)	Acrofronto-facionasal dysostosis/OMIM 616462	None	Trio WES	CS	FB/CHLA	d
17	NFIX	AD (de novo)	Marshall–Smith syndrome+glioma/OMIM 602535+Pheno. exp.	None	Trio WES	CS	FB/CHLA	d
18	FBN2	AD (de novo)	Congenital contractural arachnodactyly/OMIM 121050	None	Trio WES	CS	FB/CHLA	d
19	DCHS1	AR	Van Maldergem syndrome 1 / OMIM 601390+Phen Exp.	K, Panel	Trio WES	CS	FB/BCH	d
20	ALX1	AR	Frontonasal dysplasia-microphthalmia-facial clefting/OMIM 613456	None	Trio WES	CS	FB/MGH	In prep.
21	CDH1	AD	Blepharocheilodontic Syndrome 1/OMIM 119580	None	Pbd, M WES	CC, MC	FB/CHLA	d
22	CNTNAP1	AR	Lethal congenital contracture syndrome 7/OMIM 616286	MA	Quad WES	CC	HUDN/MGH	FE
23	MAGEL2	AD (de novo)	Schaaf–Yang syndrome/OMIM 614547	MA, K	Trio WES	CS	HUDN/BCH	Closed
24	PAX6 b	AD (de novo)	Aniridia plus clubfoot, craniofacial disorder/OMIM 106210+Pheno. exp.	Micro	Trio WES	CS	FB/CHLA	d
25	EPCAM	AR	Pancreatic insufficiency, global developmental delay/OMIM 613217	Panel	Trio WES	CS	HUDN/BCH	Closed
26	SNTA1	AD	Isolated hypoparathyroidism/novel	None	Pbd, c WES	CS	MGH/Endocrin	FE
27	TRPV4	AR	Distal hereditary motor neuropathy/OMIM 606071+Pheno. Exp.	None	Trio WES	CC	BCH/MCODR	FE
28	ITGB2 c	AD	Purpura fulminans/novel	None	Cohort WES	CS, MC, FE	UIHC	FE
29	MED12 b	XLR	Congenital anomalies, polydactyly/some similarity to OMIM 300895	MA, FISH	Trio WGS	CS	HUDN/BCH	FE
30	MED13L	AD (de novo)	Pierre Robin syndrome, ASD/OMIM 616789	MA, FISH, K	Trio WES	CS	FB/UCSF	https://www.facebase.org/ d

Note that for HUDN cases, only cases solved independently by BGM are listed. Mutational data and case details are available upon request

AR autosomal recessive, AD autosomal dominant, cons consanguineous pedigree, MA microarray, K karyotype, Panel gene panel and/or individual gene tests, FISH fluorescence in situ hybridization, WES whole-exome sequencing, WGS whole-genome sequencing, Pbd proband, c cousin(s), s sib(s), re-anly re-analysis, M mother, F father, S segregation analysis, Trio proband M, F, CS crowdsourcing, CC case champion, MC multiple cases, MO model organism, FE functional experiments (completed or ongoing), BWH Brigham and Women’s Hospital, BCH Boston Children’s Hospital, MGH Massachusetts General Hospital, DGAP Developmental Genome Anatomy Project, FB NIDCR FaceBase Consortium, KFSH King Faisal Specialist Hospital and Research Center, FCC Feingold Center for Children, CHLA Children’s Hospital Los Angeles, HUDN Harvard Undiagnosed Disease Network-Clinical Site, UIHC University of Iowa Hospitals and Clinics, UHF University of Florida Health, MCODR Manton Center for Orphan Disease Research, Rheum rheumatology, Cardio cardiovascular medicine, GI gastroenterology, Allergy & Imm allergy and immunology, Endocrin endocrinology

^aPossible digenic inheritance, based on phenotype

^bMay not explain entire phenotype

^cPotential synthetic enhancement of phenotype due to genetic interaction with additional loci within in the same functional pathway

^dDe-identified genomic sequences and clinical data available via the NIDCR FaceBase Hub website (https://www.facebase.org/) contingent upon approval